Re: [ccp4bb] [3dem] Which resolution?

[Gerard Bricogne]

Gentlemen,

 Please consider for a moment that by such intemperate language and
tone, you are making a topic of fundamental importance to both the MX and
the EM communities into a no-go area. This cannot be good for anyone's
reputation nor for the two fields in general. It has to be possible to
discuss the topic of "resolution" in a dispassionate way, so as to jointly
gain an improved and shared understanding of the matter, without feeling
implicitly under pressure to support one side or the other. An acrimonious
dispute like this one can only be putting people off getting involved in the
discussion, which is exactly the opposite of what a thread on a scientific
bulletin board should be doing.


 With best wishes,

  Gerard.

--
On Sun, Feb 23, 2020 at 08:15:34AM -0300, Marin van Heel wrote:
> Hi Carlos Oscar and Jose-Maria,
> 
> I choose to answer you guys first, because it will take little of my time
> to counter your criticism and because I have long since been less than
> amused by your published, ill-conceived criticism:
> 
> “*Marin, I always suffer with your reference to sloppy statistics. If we
> take your paper of 2005 where the 1/2 bit criterion was proposed, Eqs. 4 to
> 15 have completely ignored the fact that you are dealing with Fourier
> components, that are complex numbers, and consequently you have to deal
> with random variables that have TWO components, which moreover the real and
> imaginary part are not independent and, in their turn, they are not
> independent of the nearby Fourier coefficients so that for computing radial
> averages you would need to account for the correlation among coefficients*”
> 
> I had seen this argumentation against our (2005) paper in your
> manuscript/paper years back. I was so stunned by the level of
> misunderstanding expressed in your manuscript that I chose not to spend any
> time reacting to those statements. Now that you choose to so openly display
> your thoughts on the matter, I have no other choice than to spell out your
> errors in public.
> 
> 
> 
> All complex arrays in our 2005 paper are Hermitian (since they are the FTs
> of real data), and so are all their inner products. In all the integrals
> over rings one always averages a complex Fourier-space voxel with its
> Hermitian conjugate yielding *ONE* real value (times two)!  Without that
> Hermitian property, FRCs and FSCs, which are real normalised correlation
> functions would not even have been possible. I was - and still am - stunned
> by this level of misunderstanding!
> 
> 
> 
> This is a blatant blunder that you are propagating over years, a blunder
> that does not do any good to your reputation, yet also a blunder that has
> probably damaged to our research income. The fact that you can divulgate
> such rubbish and leave it out there for years for referees to read (who are
> possibly not as well educated in physics and mathematics) will do – and may
> already have done – damage to our research.  An apology is appropriate but
> an apology is not enough.
> 
> 
> 
> Maybe you should ask your granting agencies how to transfer 25% of your
> grant income to our research, in compensation of damages created by your
> blunder!
> 
> 
> 
> Success with your request!
> 
> 
> 
> Marin
> 
> 
> 
> PS. You have also missed that our 2005 paper explicitly includes the
> influence of the size of the object within the sampling box (your: “*they
> are not independent of the nearby Fourier coefficients*”). I remain
> flabbergasted.
> 
> On Fri, Feb 21, 2020 at 3:15 PM Carlos Oscar Sorzano 
> wrote:
> 
> > Dear all,
> >
> > I always try to refrain myself from getting into these discussions, but I
> > cannot resist more the temptation. Here are some more ideas that I hope
> > bring more light than confusion:
> >
> > - There must be some functional relationship between the FSC and the SNR,
> > but the exact analytical form of this relationship is unknown (I suspect
> > that it must be at least monotonic, the worse the SNR, the worse FSC; but
> > even this is difficult to prove). The relationship we normally use
> > FSC=SNR/(1+SNR) was derived in a context that does not apply to CryoEM (1D
> > stationary signals in real space; our molecules are not stationary), and
> > consequently any reasoning of any threshold based on this relationship is
> > incorrect (see our review).
> >
> > - Still, as long as we all use the same threshold, the reported
> > resolutions are comparable to each other. In that regard, I am happy that
> > we have set 0.143 (although any other number would have served the purpose)
> > as the standard.
> >
> > - I totally agree with Steve that the full FSC is much more informative
> > than its crossing with the threshold. Specially, because we should be much
> > more worried about its behavior when it has high values than when it has
> > low values. Before crossing the threshold it should be as high as possible,
> > and that is the "true measure" of goodness of the map. When it c

Re: [ccp4bb] [ccpem] [3dem] Which resolution?

[Gerard Bricogne]

Dear Sjors,

 I am happy to oblige as the forwarding agent.

 Thank you for continuing this thread: I hope others will do so as well.
These questions are too important to be lost to polemics fatigue ... .


 With best wishes,

  Gerard.

- Forwarded message from Sjors Scheres  -

Date: Mon, 24 Feb 2020 09:48:06 +
From: Sjors Scheres 
Subject: Re: [ccpem] [3dem] Which resolution?
To: cc...@jiscmail.ac.uk

Dear all,

For the newcomers to the cryo-EM field who may be more familiar with X-ray
crystallography and who may not be familiar with this longstanding discussion,
five observations:

1) For large numbers of Fourier components per shell, the FSC=0.143 criterion
is correct and equivalent to the FOM=0.5 criterion used in protein
crystallography. From personal experience in RELION it has worked well in
terms of expected behaviour: alpha-helices become tubular densities around
9-10A, beta-strands become separated at 4.7A, RNA base pairs at 3.6A, etc.

2) Marin is correct that there is an argument for a variable threshold over a
fixed one: when the number of (independent) Fourier components per shell drops
(because the shell lies closer to the origin of the Fourier transform, i.e. is
at lower spatial frequency; or in case of symmetry) one needs to raise the
threshold.

3) However, the amount by how much the threshold changes for typically cases
does, in my opinion, not warrant the language used to make point 2) every
other year or so. Please see here
https://twitter.com/SjorsScheres/status/935182696325763072/ for a plot of the
frequency-dependent behaviour of the 1/2-bit criterion (without symmetry). It
asymptotically approaches 0.172. It was chosen (somewhat arbitrarily) over the
twice as large 1-bit criterion because it was closer to 0.143. However, for a
typical case where the diameter of the particle D is half the box size L (see
Marin's paper here:
https://www.sciencedirect.com/science/article/pii/S1047847705001292)
the
1/2-bit criterion deviates less from 0.172 than 0.172 itself deviates from
0.143 for any Fourier shell that is more than 25 shells away from the origin.
So, for typical single-particle reconstructions with box sizes of say 200-400
pixels used nowadays, and resolutions around say half-Nyquist, the
frequency-dependent threshold will affect the resolution estimate very little,
or at least much less than the arbitrariness in the 1/2-bit criterion itself.
Perhaps someone should propose to multiply the 1/2-bit curve by 0.83 so that
one gets a frequency-dependent threshold that asymptotically reaches 0.143?
;-)

4) There are cases where the frequency-dependent threshold does become more
relevant, e.g. for very low resolutions or when using much smaller box sizes.
The latter occurs for example in sub-tomogram averaging or in (I suspect)
methods some people use for local-resolution calculation.

5) The estimated overall resolution based on whatever FSC-criterion you favour
is just a number. Besides different criteria, there are also subtle
differences in the way different programs calculate the half-maps and correct
for masking effects on the FSC curves. Therefore, don't obsess over how this
number changes in its decimal: what really matters is the quality
(interpretability) of your map.

Hope that helps,
Sjors

PS: I am not on CCP4BB, but I would be OK with someone who is forwarding this
message there.



Marin van Heel wrote:
> 
> Hi Carlos Oscar and Jose-Maria,
> 
> I choose to answer you guys first, because it will take little of my time
> to counter your criticism and because I have long since been less than
> amused by your published, ill-conceived criticism:
> 
> “*/Marin, I always suffer with your reference to sloppy statistics. If we
> take your paper of 2005 where the 1/2 bit criterion was proposed, Eqs. 4
> to 15 have completely ignored the fact that you are dealing with Fourier
> components, that are complex numbers, and consequently you have to deal
> with random variables that have TWO components, which moreover the real
> and imaginary part are not independent and, in their turn, they are not
> independent of the nearby Fourier coefficients so that for computing
> radial averages you would need to account for the correlation among
> coefficients/*”//
> 
> I had seen this argumentation against our (2005) paper in your
> manuscript/paper years back. I was so stunned by the level of
> misunderstanding expressed in your manuscript that I chose not to spend
> any time reacting to those statements. Now that you choose to so openly
> display your thoughts on the matter, I have no other choice than to spell
> out your errors in public.
> 
> All complex arrays in our 2005 paper are Hermitian (since they are the FTs
> of real data), and so are all their inner products. In all the integrals
> over rings one always averages a complex Fourier-space voxel with its
> Hermitian conjugate yielding */O

[ccp4bb] An error in the IUCr Online Dictionary of Crystallography

[Gerard Bricogne]

Dear all,

 While we are all discussing how to "push the frontiers" of our field,
there seem to be some dark and dusty corners in the documentation of some
basic notions. For instance the formula for the real-space correlation
coefficient given at 

 https://dictionary.iucr.org/Real-space_correlation_coefficient

is completely garbled. The absolute value signs in the denominator are
superfluous, although harmless since we are dealing with real numbers, but
the numerator is wrong in two respects:

 1. there should not be absolute values around the deviations from the
mean of the two types of densities;

 2. the expression should be a single summation of products of those two
types of deviation, not a product of single sums!

Does anyone know how to get this corrected?


 With best wishes,

  Gerard.



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Re: [ccp4bb] [g...@globalphasing.com: [ccp4bb] An error in the IUCr Online Dictionary of Crystallography] (fwd)

[Gerard Bricogne]

Dear Brian,

 Thank you for your reply. I think I could have provided you with the
correct formula myself ;-) but it is indeed correct now. In any case, the
verbal description I gave in my message specified it already.

 The definition in the mmCIF dictionary does look like the source of
that aberrant formula. Is it actually used somewhere as defined? That would
be scary.

 In any case, the one formula in the paper by Jones et al. cited in the
mmCIF description is a real-space R-factor, not a real-space correlation
coefficient. Some sort of monstrous recombination seems to have taken place
between the formula for an R-factor and that for a correlation coefficient,
giving rise to the eye-popping formula I spotted.

 I hope you won't mind if I post this reply to the CCP4BB again, just
for its general entertainment value. It isn't every day that one comes
across this type of typesetting hybridisation :-))) .


 With best wishes,

  Gerard.

--
On Tue, Mar 10, 2020 at 05:39:54PM +, Brian McMahon wrote:
> Dear Gerard
> 
> I've made an amendment following a version of the equation sent
> separately by Randy Read. Please review and let me know if that is
> satisfactory.
> 
> This error seems to have arisen from a transcription of a definition in the
> mmCIF/PDBx dictionary 
> (http://mmcif.pdb.org/dictionaries/mmcif_pdbx_v50.dic/Items/_struct_mon_prot.RSCC_all.html)
> which will also need updating. I'll follow that up.
> 
> Thanks for bringing this to our attention.
> 
> Best wishes
> Brian
> 
> 
> On 10/03/2020 17:11, Gerard Bricogne wrote:
> > Dear Brian,
> > 
> >   Sorry to have taken this matter up in such a visible manner: I noticed
> > this very wrong formula in someone's paper, and that person then told me
> > where he had found it. Having landed on that page, I didn't know where to go
> > next. I can't create an account because I do not have an entry in the World
> > Directory of Crystallographers.
> > 
> >   What is the best way of getting this formula corrected?
> > 
> > 
> >   With best wishes,
> > 
> >Gerard.
> > 
> > - Forwarded message from Gerard Bricogne  -
> > 
> > Date: Tue, 10 Mar 2020 14:15:33 +
> > From: Gerard Bricogne 
> > Subject: [ccp4bb] An error in the IUCr Online Dictionary of Crystallography
> > To: CCP4BB@JISCMAIL.AC.UK
> > 
> > Dear all,
> > 
> >   While we are all discussing how to "push the frontiers" of our field,
> > there seem to be some dark and dusty corners in the documentation of some
> > basic notions. For instance the formula for the real-space correlation
> > coefficient given at
> > 
> >   https://dictionary.iucr.org/Real-space_correlation_coefficient
> > 
> > is completely garbled. The absolute value signs in the denominator are
> > superfluous, although harmless since we are dealing with real numbers, but
> > the numerator is wrong in two respects:
> > 
> >   1. there should not be absolute values around the deviations from the
> >  mean of the two types of densities;
> > 
> >   2. the expression should be a single summation of products of those 
> > two
> >  types of deviation, not a product of single sums!
> > 
> > Does anyone know how to get this corrected?
> > 
> > 
> >   With best wishes,
> > 
> >Gerard.
> > 
> > 
> > 
> > To unsubscribe from the CCP4BB list, click the following link:
> > https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1
> > 
> > - End forwarded message -
> > 



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Re: [ccp4bb] [g...@globalphasing.com: [ccp4bb] An error in the IUCr Online Dictionary of Crystallography] (fwd)

[Gerard Bricogne]

Dear all,

 I don't quite know what to say about the direction in which the initial
topic is getting derailed ... .

 The substance of it is that an official (IUCr) online definition of a
statistic very much relied upon contained both a mathematical error and an
erroneous verbal description, and that this was promptly corrected through
an immediate mobilisation of good will (thank you Randy and Brian).

 Why not leave it at that?


 With best wishes,

  Gerard.

--
On Wed, Mar 11, 2020 at 04:53:25PM +, Eleanor Dodson wrote:
> Am I missing something? He? She? It? Are they now interchangeable?
> 
> On Wed, 11 Mar 2020 at 16:15, Tim Gruene  wrote:
> 
> > Dear Gerard,
> >
> > you are wrong. 'he'  in this context has as much information as 'someone'
> > and
> > 'person'. It does not refer to the sex of the person spoken about.
> >
> > Best regards,
> > Tim
> >
> > On Wednesday, March 11, 2020 4:44:47 PM CET Gerard DVD Kleywegt wrote:
> > > >>>   Sorry to have taken this matter up in such a visible manner: I
> > > >>>   noticed
> > > >>>
> > > >>> this very wrong formula in someone's paper, and that person then
> > told me
> > > >>> where he had found it. Having landed on that page, I didn't know
> > where
> > > >>> to go
> > > For the students:
> > >
> > > "someone" = systematic absence of information = 0 bits
> > > "person" = systematic absence of information = 0 bits
> > > "he" = 1 bit of information!
> > >
> > > --The other Gerard (1 bit of information!)
> > >
> > > **
> > > Gerard J. Kleywegt
> > >
> > >http://xray.bmc.uu.se/gerard   mailto:ger...@xray.bmc.uu.se
> > > **
> > > The opinions in this message are fictional.  Any similarity
> > > to actual opinions, living or dead, is purely coincidental.
> > > **
> > > Little known gastromathematical curiosity: let "z" be the
> > > radius and "a" the thickness of a pizza. Then the volume
> > >  of that pizza is equal to pi*z*z*a !
> > > **
> > >
> > > 
> > >
> > > To unsubscribe from the CCP4BB list, click the following link:
> > > https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1
> >
> > --
> > --
> > Tim Gruene
> > Head of the Centre for X-ray Structure Analysis
> > Faculty of Chemistry
> > University of Vienna
> >
> > Phone: +43-1-4277-70202
> >
> > GPG Key ID = A46BEE1A
> >
> > 
> >
> > To unsubscribe from the CCP4BB list, click the following link:
> > https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1
> >
> 
> 
> 
> To unsubscribe from the CCP4BB list, click the following link:
> https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1



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[ccp4bb] Raw diffraction images for SARS-CoV-2 related structures

[Gerard Bricogne]

Dear colleagues,

Perusal and some initial (re-)refinement of the various SARS-CoV-2 protease
structures in the PDB seems to indicate that that there might be potential
to improve these if refinements could be repeated after some reprocessing
and further analysis of the raw diffraction images, rather than against the
deposited merged data. This statement should in no way be construed as a
criticism of the remarkable achievements of the research groups concerned,
who have been operating under tremendous time pressure, but as an exciting
opportunity to push methods to their limits on a uniquely significant class
of structures.

Another consideration is that the various logistical problems created by
COVID-19 may soon make it increasingly difficult to collect new diffraction
data on potential drug targets relevant to the fight against SARS-CoV-2,
underlining the importance of ensuring that the best results be obtained
from every dataset actually collected, and that the most useful conclusions
be drawn from the analysis of those datasets towards improving the quality
of subsequent data collections. 

On this basis we would like to propose that special efforts be made to grant
public access to the raw image data associated with any SARS-CoV-2 related
structure that is deposited into the PDB. This can be done by (1) archiving
these raw image data using resources such as data.sbgrid.org, zenodo.org,
proteindiffraction.org or any other cloud-based data-sharing service, and
(2) communicating the corresponding DOIs to the wwPDB centres. This idea
could be extended to datasets that investigators would like to offer to
interested methods developers or expert users at the pre-deposition stage.

Experts making use of those raw data would be encouraged to document, in as
much detail as possible, how particular programs or workflows could be used
on those structures/datasets to obtain the best results. This would be a
kind of "virtual workshop", a particularly valuable collective activity at
the present time when several in-person workshops (e.g. RapiData) have been
cancelled and many meetings are in limbo for several months.

The latter activity would benefit from having a centralised facility set up
for the experts to post their results and annotations: we could create such
a facility, but other, larger groups might want to consider doing so. 


With best wishes,

Clemens & Gerard.



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[ccp4bb] Raw diffraction images for SARS-CoV-2 related structures

[Gerard Bricogne]

Dear all,

 It is a pleasure to be able to end the (GMT) week by calling for a huge
round of applause for the Diamond team, who this afternoon started uploading
a large collection of sets of raw diffraction images (77 as we write but the
upload is still ongoing) for PDB entries that were released two days ago.

 Special thanks to Graeme Winter who organised the upload to Zenodo. The
datasets are collectively accessible via the following link:

https://zenodo.org/search?page=1&size=20&q=keywords:%22SARS-CoV-2%20main%20protease%22

 Graeme asked that "major kudos [be given] to Zenodo developers who have
been very responsive with helping us do automated downloads".

 Happy scrutiny and reprocessing of these datasets, and re-refinement of
the associated structures, to all hard-core MX addicts!


 With best wishes,

 Clemens & Gerard.

--
On Thu, Mar 19, 2020 at 10:00:11AM +, John Berrisford wrote:
> Dear all
> 
> The wwPDB OneDep system allows depositors to provide DOIs of raw
> diffraction images during deposition to the PDB and once again
> encourages depositors to provide a DOI for raw images when they have
> submitted.  
> 
> Out of the 9665 X-ray entries that were released in 2019 we have DOI's
> for raw images in 205 of these entries.  
> 
> We would encourage depositors to provide the DOI for their raw images
> when they are available.  
> 
> Regards
> 
> John
> 
> 
> On Mar 19 2020, at 9:48 am, Joel Sussman  wrote:
> 
> > 19-Mar-2020
> > Dear Loes, Peter, Clemens & Gerard,
> > I concur that it is crucial to preserve the original diffraction data
> > and make it available to anyone who would like to use it.
> > As an example, please see the very recent paper by 
> > Nachon et al (2020). "A second look at the crystal structures of
> > Drosophila melanogaster acetylcholinesterase in complex with tacrine
> > derivatives provides Insights concerning catalytic intermediates and
> > the design of specific insecticides" Molecules 25 pii: E1198 
> > [https://www.ncbi.nlm.nih.gov/pubmed/32155891].
> > The study reexamines the original data, with modern software tools,
> > the original data of a paper we published in 2000 (~20 years ago) and
> > revealed features that had not been noticed. Specifically 
> > 1) previously unmodeled density in the native active site can be
> > interpreted as stable acetylation of the catalytic serine. 
> > 2) Similarly, a strong density in the DmAChE/ZA complex, originally
> > attributed to a sulfate ion, is better interpreted as a small molecule
> > that is covalently bound. The complex is reminiscent of the
> > carboxylate/BChE complexes observed in crystal structures of hBChE
> > [Brazzolotto et al, 2012; Nicolet et al, 2003], and demonstrates the
> > remarkable ability of ChEs to stabilize covalent complexes with 
> > carboxylates.
> > Thus, the study demonstrates that updated processing of older
> > diffraction images, and the re-refinement of older diffraction data,
> > can produce valuable information that could not be detected in the
> > original analysis, and strongly supports the preservation of the
> > diffraction images in public data banks.
> > Best regards
> > Joel
> > 
> > Prof. Joel L. Sussman.        joel.suss...@weizmann.ac.il   
> > www.weizmann.ac.il/~joel
> > Dept. of Structural Biology   tel: +972  (8) 934 6309       proteopedia.org
> > Weizmann Institute of Science fax: +972  (8) 934 6312
> > Rehovot 76100 ISRAEL          mob: +972 (50) 510 9600
> > -
> >  
> >  
> >> On 19 Mar 2020, at 11:32, Kroon-Batenburg, L.M.J. (Loes)
> >>  wrote:
> >>  
> >> Dear Gerard,
> >>  
> >> This is a great idea. Of course I am very much in favour of making
> >> available raw diffraction images, and such a virtual workshop could
> >> demonstrate the usefulness of reprocessing raw diffraction data and
> >> structural refinements. I am not at all afraid that archiving of raw
> >> data that are the basis of a scientific paper will have significant
> >> environmental effects: this is minor compared to our everyday use of
> >> cloud services.  And as Graeme mentioned: when archiving raw data
> >> make sure to add sufficient and correct meta data.
> >>  
> >> Best wishes,
> >> Loes
> >>  
> >> ___
> >> Dr. Loes Kroon-Batenburg
> >&g

Re: [ccp4bb] Jean-Luc Ferrer

[Gerard Bricogne]

Dear all,

 This is very sad news indeed and Jean-Luc's passing away is an enormous
loss for the crystallographic community at large. He and his team showed a
capacity for innovation that stretched over two decades, with the creation
of in situ crystallography (the idea came from Alex McPherson but it was
Jean-Luc who first made it into a production resource on his FIP beamline)
and of the CATS sample changer that adorns most MX synchrotron beamlines
today, later perfected into the versatile multi-purpose G-Rob system. 

 These instrumental innovations entailed very significant software
developments, and it is remarkable that with limited resources and staff
size, his FIP group was able to stand at the forefront of the early creation
of automated data processing pipelines connected to a live data collection
facility.

 Jean-Luc's ground-breaking work on in-situ data collection and the high
level of automation of such experiments (using e.g. his "Crystal Listing")
was the direct precursor of today's High-Throughput Ligand Screening by MX
(e.g. the Diamond VMX-i beamline) and of Synchrotron Serial Crystallography.

 A (very) short anthology of my own favourites among his papers:

https://journals.iucr.org/d/issues/2001/11/00/li0408/index.html
https://journals.iucr.org/j/issues/2004/01/00/hx5003/index.html
https://journals.iucr.org/j/issues/2013/03/00/rg5033/index.html
https://journals.iucr.org/d/issues/2015/08/00/jm5007/index.html

(no attempt here at being exhaustive, nor at writing an obituary ...).

 Jean-Luc's energy, creative power and spirit of enterprise are a
welcome reminder of how much can be achieved by a small team of dedicated
members, even on a road typically dominated by juggernauts. 

 I had immense respect for him, and will miss him terribly. Most trips I
made to Grenoble were an opportunity, to which I always looked forward, to
travel early enough in the day to meet Jean-Luc for dinner and catch up with
his always original and knowledgeable views on "the state of the art" in MX.


 With deepest sympathy for his family, friends and colleagues,

  Gerard.

--
On Thu, Apr 23, 2020 at 10:19:03PM +0200, David Cobessi wrote:
> It is with a deep sadness that we learned the passing away of our dear
> colleague and friend, Dr Jean-Luc Ferrer, on April 21st in Grenoble, after a
> long struggle against his disease.
> Jean-Luc was an internationally known and highly respected scientist in
> protein crystallography.Jean-Luc had led the Synchrotron Group (GSY) at the
> IBS, a research group bridging instrumental and methodological development
> in large research infrastructures and structural biology projects. He was in
> charge of the French national (CRG) beamline FIP-BM30A at the ESRFsince
> 2001. He has always been inventive, dynamic and determined to highlight the
> advantages of synchrotron radiation for protein crystallography. Pioneer in
> the automation of crystallography beamlines, he has been the driving force
> to develop the first sample loader based on a robotic arm with the idea of
> using it directly as a goniometer. This paved the way to “in plate”
> diffraction experiments and its use for intensive ligand screening. He was
> also a co-funder of the NatX-ray company in Grenoble and San Diego and was
> strongly involved in several teaching programs and international workshops.
> Since the shutdown of the ESRF to complete its latest upgrade program,
> Jean-Luc had been in charge to rebuild the FIP beamline in order to provide
> the best service to the community, which will become BM07-FIP2.
> Jean-Luc will be forever missed and remembered.
> David Cobessi, on the behalf of the whole IBS staff and the RéNaFoBiS
> network members
> 
> 
> 
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-- 

 =======
 * *
 * Gerard Bricogne g...@globalphasing.com  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
 * *
 ===



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[ccp4bb] Micro-ED "pushing the frontiers" again ... but which frontiers?

[Gerard Bricogne]

Dear all,

 There have been warnings circulating for quite some time now about the
possible impact of SARS-CoV-2 on the cognitive abilities of patients who
have recovered from Covid-19, and I fear that I have reasons to worry about
possibly having fallen victim to these ... .

 I came across a remarkable piece of work published in 

https://doi.org/10.1016/j.str.2020.01.008

entitled "Experimental Phasing of MicroED Data Using Radiation Damage". I
will follow my notes, in order to ensure that I do not stray even further
from the logic of this paper than I may have done already in writing them
down.

 The subject matter of this article is a famous seven-residue peptide of
exceptional structural stability (which is why it is associated with severe
pathologies), giving radiation-hard microcrystals capable of yielding 1.0
Angs resolution electron diffraction data enabling the solution of this (in
effect, small-molecule) structure by direct methods (PDB code 6CLI) from
such data. A thorough study of radiation damage had been conducted on these
crystals in a previous paper (https://doi.org/10.1016/j.str.2018.03.021),
revealing a detailed picture of site-specific radiation damage affecting in
particular the fully-occupied Zn atom co-crystallised with the peptide.

 The material presented in this new paper is a by-product of the earlier
analysis at 1.0 Angs resolution, whereby two datasets were assembled to
correspond to two substantially different stages of radiation damage (PDB
codes 6CLI and 6CLJ) and were truncated to 1.4 Angs to make direct methods
ineffective. The question is then whether this differential radiation damage
can be exploited as a source of experimental phase information, as has been
done successfully with the so-called RIP method in X-ray crystallography,
the implication being that this could then constitute a generally applicable
method for experimentally phasing electron diffraction data. This ambition
is clearly articulated in the last paragraph of the Introduction: "Here, we
demonstrate that radiation damage from exposure to the electron beam can be
used to solve the phase problem in Micro-ED experiments".

 Enough to get you sitting on the edge of your seat ... .

 The delicate scaling between the two datasets (the first called "low
dose" and the second called "damaged" was accomplished by the DSCA method in
SHELXC so that the difference Patterson showed a single peak, interpreted as
being due to radiation damage on the Zn atom between the two datasets. As we
are in P1 this Zn atom could have been placed at the origin, but for the
sake of comparability, a difference Fourier map was computed by combining
the amplitude differences corresponding to the scaled intensities with the
phases from 6CLI, in which the highest peak corresponded to the position of
the Zn atom in 6CLI. 

 Now the heart of the matter. The maps produced from this single Zn as
sole source of phase information were uninterpretable. Density modification
did not help, presumably because these crystals are close-packed so that
there is no solvent to flatten. The method used instead in order to "solve
the phase problem" (sic) consists in placing atoms in trial positions and
applying some selection criteria to prune out the worst choices. None of
these criteria, however, can dispense with using the wMPE (weighted mean
phase error) from the known structure (6CLI) as a guide. In whatever way it
may be described, therefore, the procedure used seems depends on already
knowing the perfect structure from the previous work at 1.0 Angs resolution.

 This is where I began to question my own sanity, and to wonder whether,
like Rip van Winkle (https://en.wikipedia.org/wiki/Rip_Van_Winkle), I had
somehow fallen into a deep sleep and completely missed a revolution: I was
still clinging to the old-fashioned conception of experimental phasing as
the technique that has the power to produce three-dimensional electron
density maps for macromolecules with total objectivity; now, however, the
new paradigm is clearly that the "experimental" component in experimental
phasing consists in experimenting with the trial placement of atoms while
keeping an eye on the agreement between the corresponding phases and those
for ... the already known structure!

 The problem must obviously lie on my side, since this work has been
published not only in the highly-respected journal "Structure", but even
under the prestigious "Resource" label of this journal, reserved for
articles that are expected "to highlight significant technical advances,
exciting new methods [...] that are of value and interest to the broad
Structure readership and have high impact on the field of structural
biology". 

 I can see that it should indeed have some impact, in the sense of
reassuring Structure readers that if they too happen to have pathologically
stable crystals capable of diffracting to 1.0 Angs resolution (so that, when

Re: [ccp4bb] Highest resolution of X-ray / neutron / electron crystallography, cryo EM

[Gerard Bricogne]

Dear Tobias,

 Thank you for identifying the 0.6A resolution structure solved by
electron diffraction as 6KJ3. This is a good, genuine de novo structure
determination using direct methods (SHELXD) on high-resolution data. The
R-values are not flattering (above 30%) but one can't expect too much in
that respect when the data have a mean I/sig()I ~ 4 .

 However, looking at the chemical nature of this molecule, its sequence
is SER-TYR-SER-GLY-TYR-SER, so is it really a macromolecule? It would have
been called a hexapeptide if it had been solved by X-ray crystallography.


 With best wishes,

  Gerard.

--
On Tue, Jun 09, 2020 at 04:11:40PM +0200, Tobias Beck wrote:
> Dear all,
> 
> Thanks a lot! (I should have used the PDB query myself for neutrons, sry,
> my bad)
> 
> As there was a request to share the bioRxiv links, here they are:
> https://www.biorxiv.org/content/10.1101/2020.05.21.106740v1
> https://www.biorxiv.org/content/10.1101/2020.05.22.110189v1
> 
> along with the comment in Nature (which also has both links to the papers
> in the references section):
> https://www.nature.com/articles/d41586-020-01658-1
> 
> So:
> X-ray at 0.48 A
> Neutron at 0.93 A (hybrid with X-ray) or 1.05 A
> Cryo EM 1.25 A
> electron diffraction 0.6 A
> 
> Thanks to all of you!
> 
> Best, Tobias.
> 
> 
> On Tue, Jun 9, 2020 at 3:46 PM Tobias Beck  wrote:
> 
> > Dear all,
> >
> > Thanks for the link to the latest BioRxiv papers! So for cryo EM it is 1.2
> > now. Any numbers for neutron?
> >
> > Best, Tobias.
> >
> > Tobias Beck  schrieb am Di. 9. Juni 2020 um 15:35:
> >
> >> Dear all,
> >>
> >> I was asked by a student what the highest resolution is, for each of the
> >> four methods listed above. Maybe someone has researched the current numbers
> >> previously and would like to share them? For X-ray, I found 0.48 A in the
> >> PDB. For EM method details, the PDB gives me 0.6 A, but it is actually for
> >> electron diffraction. I found a structure with 1.8 A for Cryo EM.
> >>
> >> I am aware that resolution is only one parameter and that high resolution
> >> may not correspond to high data quality. However, maybe someone knows the
> >> record holders, either for biomacromolecules or small molecules or for
> >> both.
> >>
> >> Thanks!
> >>
> >> Best, Tobias.
> >>
> >>
> >>
> >>
> 
> 
> 
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Re: [ccp4bb] Ideas for improving refinement with anisotopic data.

[Gerard Bricogne]

Dear Matthew,

 You seem to have been unlucky with this data collection. STARANISO
would be prepared to see significant data extending to 2.0A along a*, 2.7A
along b*, and 1.7A along c*. The latter limit, however, involves some guess
work via the fitting by an ellipsoid of a cut-off surface that is very much
perturbed by the fact that you have a both a cusp and a truncation by the
detector edges in that direction. Without those, it looks quite probable
that you would have good solid data extending beyond 1.6A - if only you
could redo the experiment in such a way as to actually measure them ;-) .

 As Eleanor said, it is a bad idea to make decisions about data on the
basis of the "downstream" criteria you were mentioning. STARANISO is not
just a numerical program that estimates numbers and suggests some sensible
actions that it will carry out for you: it is also a 3D visualisation tool
that shows you much more about your data and its possible shortcomings than
any Table1-style numbers ever will. If there are indeed deficiencies in the
data, like here, these 3D pictures will often point out what shortcomings in
your experiment are responsible for them. In that case, a new experiment, if
feasible, is always better than any surgery on the deficient data.

 Please feel free to get in touch off-line if you would like more
details, such as patterns of outliers that we have observed.


 With best wishes,

 The STARANISO developers.

--
On Sun, Jun 21, 2020 at 05:33:53PM +0100, Eleanor Dodson wrote:
> *Please* dont throw good 1.8A data for the sake of statistics!
> You should see more detail along certain directions
> You will publish your structure providing honest details of the anisotropy
> (I hope..) but it is the map quality that matters ..
> Eleanor
> 
> On Sun, 21 Jun 2020 at 15:16, Matthew Snee <
> matthew.s...@postgrad.manchester.ac.uk> wrote:
> 
> > Hi everyone.
> >
> > I have an x ray structure that I am finishing up, and there are a few
> > ambiguous regions where the peptide is poorly resolved.
> >
> > The data is highly anisotrophic, and requires truncation to around 2.4A to
> > achieve acceptable merging stats, although there is data in the "good"
> > direction going as high as 1.8-1.9A (determined by merging stats when using
> > elliptical cutoff).
> >
> > I have tried feeding my integration outputs to STARANISO with both the
> > elliptical and spherical cutoffs, but neither produce better results than
> > Xia2 Dials, as both need to be truncated further than 2.3A before they give
> > the same refinement stats (i.e it's best to just let refmac/phenix.refine
> > deal with the anistropy).
> >
> > As I understand it, anisotrophy can lead to loss of high resolution detail
> > because weak observations from the high res shells in the bad direction are
> > down-weighted, So any tricks to improve map quality (or conversely refining
> > data with poor completeness) would be appreciated.
> >
> > I'm not holding out hope that I can deposit anything better than 2.3A, but
> > Improving the maps might really help me with some of these troublesome
> > loops :)
> >
> > Cheers
> >
> > Matthew.
> >
> > Sent from Outlook Mobile 
> >
> > --
> >
> > To unsubscribe from the CCP4BB list, click the following link:
> > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1
> >
> 
> 
> 
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Re: [ccp4bb] [EXTERNAL] Re: [ccp4bb] number of frames to get a full dataset?

[Gerard Bricogne]

Dear Phil,

 I would like to make an attempt to not let this question get mired in
exchanges of well-researched linguistic arguments at risk of being drowned
in a cacophony of sound bites :-) .

 You refer to the days of SCALA, at which time data were collected on
CCD detectors, whose lengthy read-out times led to designing data collection
strategies so that they would achieve completeness in the smallest number of
"frames", themselves chosen as thick-sliced as possible while avoiding
angular overlap because of the read-out noise added to each such frame. With
this mindset, measuring again a reflection that had already been measured
could have been viewed as a waste of effort, bringing water to the mill of
interpreting "redundancy" as a sign of sub-optimality. However, looking
again at the CCD datasets collected according to this paradigm, they are
dire! Minimal availability of symmetry-related measurements made internal
scaling fragile, the terrible corner effects in the 3x3 detectors could not
be corrected, and the tracking of radiation damage was beyond hope.

 A lot has happened since, namely pixel-array detectors, fine-sliced
images recorded at low transmission, aiming at recording symmetry-related
reflections "a large number of times" - whatever one ends up calling that.
Far from being superfluous, or "redundant" in the negative sense of the
term, these "abundant" measurements (to coin a phrase) are now recognised as
being absolutely crucial towards the rejection of outliers, a key process in
obtaining high-quality data. This would then bring us back to the positive,
even noble connotation of the term "redundancy", since an abundance of
symmetry-related measurements now allows the detection and rejection of the
dodgy ones. From that perspective, "redundant" is good in the sense Ian
mentioned in relation to aviation equipment: if a few of those measurements
are rotten, you can throw them away and still have some left to do the job.
If you have abundant measurements and just call them multiple, this sense of
allowing rescue in case of failure disappears, and with it an important
aspect of why one should go for strategies that harvest symmetry-related
measurement in high numbers. This is why I ceased to support the standard
term "multiplicity" in conversations with Ian and went along with his choice
of the term "redundancy" in the presentation of STARANISO results.


 With best wishes,

  Gerard.

--
On Tue, Jun 30, 2020 at 02:30:27PM +0100, Phil Evans wrote:
> I changed the annotation from “Redundancy” to “Multiplicity” in Scala, later 
> in Aimless, after I was taken to task by Elspeth Garman with the argument as 
> stated, that if it’s redundant why did you bother to measure it?
> 
> (this one could run and run …)
> 
> Phil
> 
> > On 30 Jun 2020, at 14:07, Ian Tickle  wrote:
> > 
> > 
> > I agree about RAID but I would go a lot further.  There seems to be some 
> > confusion here over the correct meaning of 'redundant' as used in a 
> > scientific context.  I don't think looking it up in an English dictionary 
> > is very helpful.  So as has been mentioned the non-scientific and rather 
> > imprecise meanings are "not or no longer needed or useful; superfluous" or 
> > "exceeding what is necessary or natural; superfluous" and "needlessly 
> > repetitive; verbose".  In fact both redundant and abundant have the same 
> > Latin etymology, and redundant literally means 're' (again) + 'unda' 
> > (wave), i.e. 'repeating as a wave'.  The original meaning in English is in 
> > fact 'over-abundant' and is still used in poetry with that meaning (e.g. 
> > "as redundant as the poppies in the field").  There's of course also the 
> > meaning 'dismissal from a job due to a need to reduce the head count' and 
> > from there 'out of work', but that's relatively recent having been coined 
> > by a UK Government official in the 1900s!
> > 
> > The correct and totally precise scientific meaning which is appropriate in 
> > the context of this discussion is to be found here: 
> > https://en.wikipedia.org/wiki/Redundancy_(engineering) .  Note that it 
> > applies equally to both hardware and software engineering:
> > 
> > Redundancy is the duplication of critical components or functions of a 
> > system with the intention of increasing reliability of the system, usually 
> > in the form of a backup or fail-safe, or to improve actual system 
> > performance.
> > 
> > Nothing there about not or no longer needed or useful, superfluous, 
> > needlessly repetitive, verbose!  Note that 'multiplicity' totally fails to 
> > carry the connotation of increasing the system reliability by duplication 
> > (i.e. there are multiple copies but there's nothing that indicates the 
> > justification for them).  Redundancy occurs in TMR (triple modular 
> > redundancy) systems used (as I guess Bernhard knows well) in triplicated 
> > control systems in commercial aircraft.  I don't know about you but I 
> > wouldn

Re: [ccp4bb] [EXTERNAL] Re: [ccp4bb] number of frames to get a full dataset?

[Gerard Bricogne]

Dear Bernhard,

 That is true, and the discrepancies between repeated measurements of
the same hkl would have to be parametrised differently from those between
symmetry-related ones (e.g. in terms of radiation damage only, while the
others would also involve absorption effects). However I am not aware that
the existing data processing programs we use actually make and exploit this
distinction.

 Going back to the initial topic of this thread, the main take-home
lesson for Murpholino should be: preoccupations about minimising the number
of frames to get completeness belong to a now obsolete age - instead use the
new paragigm of high-(redundancy/multiplicity) data collection with a low
transmission so that you can spread the dose your crystal can withstand over
the requisite angular range. No matter how you call the "abundance" property
of your final dataset, make sure it is high!

 The case of low symmetry has been mentioned: the extra guidance for
Murpolino is that if you are in P1, you will never get completeness with a
single orientation, so make sure that you use a multi-axis goniometer and
collect data in at least two sufficiently different orientations.


 With best wishes,

  Gerard.

--
On Tue, Jun 30, 2020 at 08:49:53AM -0700, Bernhard Rupp wrote:
> .…but there is a difference whether I measure the same identical hkl over 
> again or ‘preferably in more than one symmetry-equivalent position’, to quote 
> the
> 
> IUCr. So do we have a MPSR for the same reflection and a MPRR for the related 
> reflections?
> 
>  
> 
> Cacophonically yours,
> 
>  
> 
> BR
> 
>  
> 
> From: CCP4 bulletin board  On Behalf Of John R 
> Helliwell
> Sent: Tuesday, June 30, 2020 08:36
> To: CCP4BB@JISCMAIL.AC.UK
> Subject: Re: [ccp4bb] [EXTERNAL] Re: [ccp4bb] number of frames to get a full 
> dataset?
> 
>  
> 
> Dear Herman,
> 
> I think that MPR is a very neat and tidy, excellent, proposal.
> 
> Moreover it uses the word “measurements”, and we are an experimental based 
> science.
> 
> I support it.
> 
> Great.
> 
> Greetings,
> 
> John 
> 
> Emeritus Professor John R Helliwell DSc
> 
>  
> 
>  
> 
>  
> 
>  
> 
> On 30 Jun 2020, at 15:10, Schreuder, Herman /DE   > wrote:
> 
>  
> 
> Dear BB,
> 
>  
> 
> Since there does not seem a generally accepted term for the subject of this 
> discussions, and since even the IUCR scriptures do not give any guidance, I 
> would propose to introduce a completely new term:
> 
>  
> 
> Measurements per reflection or MPR
> 
>  
> 
> This term is politically neutral, should adequately describe this particular 
> statistic and is not associated with entrenched traditions at either side of 
> the Atlantic.
> 
>  
> 
> What do you think?
> 
> Herman
> 
>  
> 
>  
> 
> Von: CCP4 bulletin board   > Im Auftrag von John R Helliwell
> Gesendet: Dienstag, 30. Juni 2020 14:34
> An: CCP4BB@JISCMAIL.AC.UK  
> Betreff: [EXTERNAL] Re: [ccp4bb] number of frames to get a full dataset?
> 
>  
> 
> EXTERNAL : Real sender is owner-ccp...@jiscmail.ac.uk 
>   
> 
>  
> 
> Dear Colleagues,
> 
> In an effort to break this naming deadlock, and with Massimo and Ian not 
> showing up as yet, I checked the IUCr Dictionary.
> 
> “Redundancy“ and “Multiplicity“ are not listed.
> 
> The more generic term “Statistical Descriptors“ is though and even offers 
> Recommendations:-
> 
> http://ww1.iucr.org/iucr-top/comm/cnom/statdes/recomm.html 
> 
>  
> 
> Point 1, first sentence, fits the various wishes of this thread succinctly, 
> if not in a single word, and even not readily allowing an easy acronym. 
> 
> Greetings,
> 
> John 
> 
>  
> 
> Emeritus Professor John R Helliwell DSc
> 
>  
> 
>  
> 
> 
> 
> 
> 
> On 30 Jun 2020, at 13:11, Phil Jeffrey   > wrote:
> 
> The people that already use multiplicity are going to find reasons why it's 
> the superior naming scheme - although the underlying reason has a lot to do 
> with negative associations with 'redundant', perhaps hightened in the current 
> environment.  And conversely redundant works for many others - Graeme's 
> pragmatic defense of multiplicity actually works both ways - any person who 
> takes the trouble to read the stats table, now exiled to Supplementary Data, 
> knows what it means.  Surely, then, the only way forward on this almost 
> totally irrelevant discussion is to come up with a universally-loathed 
> nomenclature that pleases nobody, preferably an acronym whose origins will be 
> lost to history and the dusty CCP4 archives (which contain threads similar to 
> this

Re: [ccp4bb] number of frames to get a full dataset?

[Gerard Bricogne]

Dear Ed,

 Concerning your remark that "use of terms redundancy and multiplicity
to describe the same concept is by itself redundant", one could perhaps say
that redundancy is an abstract property of a dataset, while multiplicity is
a numerical attribute. Redundancy is desirable because if some measurements
turn out to be corrupted, there are spare ones to salvage completeness. In
this form it is an aspect of quality, without being in itself a numerical
entity. That property of redundancy is conferred by high multiplicity of
measurement, which is very much a numerical entity. The two terms are
threfore not redundant, but are made so in practice by the shorthand of
giving the numerical attribute the name of the abstract property it gives
rise to.

 Regarding the relation to replication, I can remember Peter Mueller's
book on refinement with SHELX quoting George Sheldrick's point that simply
repeating a measurement is of limited usefulness, because one repeats its
systematic errors, and advocating that what is truly valuable is to make
multiple measurements in conditions such that their systematic errors are
likely to be different. This diversity of conditions gives rise to what he
called "true multiplicity". There is clearly a close affinity between this
concept and that of redundancy viewed as a protection against corrupted
individual measurements.

 The essential thing, though, is not the choice of terminology but the
practical decision of abjuring the pernicious mindset alluded to by the
Subject line of this thread :-) .


 With best wishes,

  Gerard.

--
On Tue, Jun 30, 2020 at 11:19:38AM -0400, Edwin Pozharski wrote:
> Replicate is a good option with its own problems as it can be seen as
> referring to exact copy which multiple measurements clearly aren't. It does
> have an advantage of being the word used by non-crystallographers though.
> 
> As a lame attempt at joke, use of terms redundancy and multiplicity to
> describe the same concept is by itself redundant.
> 
> On Mon, Jun 29, 2020, 7:21 PM Bernhard Rupp 
> wrote:
> 
> > Ah…the rise of the replicants …
> >
> >
> >
> > https://www.youtube.com/watch?v=yWPyRSURYFQ
> >
> >
> >
> > …and don’t forget the and the Voight-Kampff Test results in Table 1.
> >
> >
> >
> > Best, BR
> >
> >
> >
> > *From:* Pierre Rizkallah 
> > *Sent:* Monday, June 29, 2020 15:46
> > *To:* b...@hofkristallamt.org; CCP4BB@JISCMAIL.AC.UK
> > *Subject:* RE: [ccp4bb] number of frames to get a full dataset?
> >
> >
> >
> > You’re missing out on a grand opportunity for iconoclasm here. Try out
> > ‘Degree of Replication’ or ‘Average Replication’ or ‘Replicate Frequency’.
> > Any other offerings!
> >
> >
> >
> > P.
> >
> > ***
> >
> > Dr Pierre Rizkallah, Senior Lecturer Structural Biology
> >
> > Institute of Infection & Immunology, Sir Geraint Evans Building,
> >
> > School of Medicine, Heath Campus, Cardiff, CF14 4XN
> >
> > email: rizkall...@cardiff.ac.ukphone: +44 29 2074 2248
> >
> > http://www.cardiff.ac.uk/people/view/126690-rizkallah-pierre
> >
> >
> >
> > *From:* CCP4 bulletin board  *On Behalf Of *Bernhard
> > Rupp
> > *Sent:* 29 June 2020 23:36
> > *To:* CCP4BB@JISCMAIL.AC.UK
> > *Subject:* Re: [ccp4bb] number of frames to get a full dataset?
> >
> >
> >
> > I think it is time to escalate that discussion to crystallographic
> > definition purists like Massimo or to a logical consistency proponent like
> > Ian who abhors definitional vacuum 😊
> >
> >
> >
> > Cheers, BR
> >
> >
> >
> > *From:* CCP4 bulletin board  *On Behalf Of *Andreas
> > Förster
> > *Sent:* Monday, June 29, 2020 15:24
> > *To:* CCP4BB@JISCMAIL.AC.UK
> > *Subject:* Re: [ccp4bb] number of frames to get a full dataset?
> >
> >
> >
> > I like to think that the reflections I carefully measured at high
> > multiplicity are not redundant, which the dictionary on my computer defines
> > as "not or no longer needed or useful; superfluous" and the American
> > Heritage Dictionary as "exceeding what is necessary or natural;
> > superfluous" and "needlessly repetitive; verbose".
> >
> >
> >
> > Please don't use the term Needless repetitivity in your Table 1.  It sends
> > the wrong message.  Multiplicity is good.
> >
> >
> >
> > All best.
> >
> >
> >
> >
> >
> > Andreas
> >
> >
> >
> >
> >
> >
> >
> > On Tue, Jun 30, 2020 at 12:03 AM James Holton  wrote:
> >
> > I have found that the use of "redundancy" vs "multiplicity" correlates
> > very well with the speaker's favorite processing software.  The Denzo/HKL
> > program scalepack outputs "redundancy", whereas scala/aimless and other
> > more Europe-centric programs output "multiplicity".
> >
> > At least it is not as bad as "intensity", which is so ambiguous as to be
> > almost useless as a word on its own.
> >
> > -James Holton
> > MAD Scientist
> >
> > On 6/24/2020 10:27 AM, Bernhard Rupp wrote:
> >
> > > Oh, and some of us prefer the word 'multiplicity' ;-0
> >
> > Hmmm…maybe n

Re: [ccp4bb] AW: [ccp4bb] [EXTERNAL] Re: [ccp4bb] number of frames to get a full dataset?

[Gerard Bricogne]

Dear Dirk,

 Aren't you for getting about radiation damage? The n measurements of
the same hkl with the same geometry would not be equivalent, although they
would enable the tracking of radiation damage without the confounding with
absorption effects that comes from considering symmetry-related hkls. I
mentioned that in my second message yesterday.

 The notion of "identical" reflections measurements is problematic for
the same reason that Heraclitus wrote (something like) "You cannot step
twice into the same river". 


 With best wishes,

  Gerard.

--
On Wed, Jul 01, 2020 at 10:46:57AM +0200, Dirk Kostrewa wrote:
> Dear Herman,
> 
> I think, your MPR proposal is a great idea and would like to second it! And
> I would also like to propose that data processing programs just average
> "identical" reflections measured under the same geometry and count them only
> once (*), so that, in the end, we will get a realistic number of truly
> independent measurements.
> 
> Cheers,
> 
> Dirk.
> 
> (*) I don't see a difference between measuring the same reflection with the
> same geometry n-times and measuring it n-times as long (apart from, maybe,
> catching instabilities in the experimental setup). Just averaging such
> "identical" reflections would simplify the subsequent scaling process with
> equivalent reflections that were measured under different geometry.
> 
> On 01.07.20 09:32, Schreuder, Herman /DE wrote:
> > 
> > Dear Bernard and other bulletin board members,
> > 
> > As Gerard mentioned, current data processing programs and table 1’s do
> > not make this distinction, but of course, you are free to ask the
> > community to introduce it.
> > 
> > My proposal to use “measurements per reflections” is not a joke. It
> > exactly describes what is meant by the parameter and it is easily
> > understood even by lay people like journal editors and referees, without
> > the need of lengthy explanations like the ones we have seen in this
> > thread.
> > 
> > I really would like to ask you to consider replacing
> > multiplicity/redundancy/abundancy by MPR. At minimum, it may prevent a
> > thread about completeness of data sets to be hijacked by a discussion on
> > whether use the name multiplicity of redundancy for the number of
> > measurements per reflection.
> > 
> > My 2 cents,
> > 
> > Herman
> > 
> > *Von:* CCP4 bulletin board  *Im Auftrag von
> > *Bernhard Rupp
> > *Gesendet:* Dienstag, 30. Juni 2020 17:50
> > *An:* CCP4BB@JISCMAIL.AC.UK
> > *Betreff:* Re: [ccp4bb] [EXTERNAL] Re: [ccp4bb] number of frames to get
> > a full dataset?
> > 
> > *EXTERNAL : *Real sender is owner-ccp...@jiscmail.ac.uk
> > 
> > 
> > .…but there is a difference whether I measure the same identical hkl
> > over again or ‘preferably in more than one symmetry-equivalent
> > position’, to quote the
> > 
> > IUCr. So do we have a MPSR for the same reflection and a MPRR for the
> > related reflections?
> > 
> > Cacophonically yours,
> > 
> > BR
> > 
> > *From:*CCP4 bulletin board  > > *On Behalf Of *John R Helliwell
> > *Sent:* Tuesday, June 30, 2020 08:36
> > *To:* CCP4BB@JISCMAIL.AC.UK 
> > *Subject:* Re: [ccp4bb] [EXTERNAL] Re: [ccp4bb] number of frames to get
> > a full dataset?
> > 
> > Dear Herman,
> > 
> > I think that MPR is a very neat and tidy, excellent, proposal.
> > 
> > Moreover it uses the word “measurements”, and we are an experimental
> > based science.
> > 
> > I support it.
> > 
> > Great.
> > 
> > Greetings,
> > 
> > John
> > 
> > Emeritus Professor John R Helliwell DSc
> > 
> > On 30 Jun 2020, at 15:10, Schreuder, Herman /DE
> > mailto:herman.schreu...@sanofi.com>>
> > wrote:
> > 
> > 
> > 
> > Dear BB,
> > 
> > Since there does not seem a generally accepted term for the
> > subject of this discussions, and since even the IUCR scriptures do
> > not give any guidance, I would propose to introduce a completely
> > new term:
> > 
> > Measurements per reflection or MPR
> > 
> > This term is politically neutral, should adequately describe this
> > particular statistic and is not associated with entrenched
> > traditions at either side of the Atlantic.
> > 
> > What do you think?
> > 
> > Herman
> > 
> > *Von:*CCP4 bulletin board  > > *Im Auftrag von *John R Helliwell
> > *Gesendet:* Dienstag, 30. Juni 2020 14:34
> > *An:* CCP4BB@JISCMAIL.AC.UK 
> > *Betreff:* [EXTERNAL] Re: [ccp4bb] number of frames to get a full
> > dataset?
> > 
> > *EXTERNAL : *Real sender is owner-ccp...@jiscmail.ac.uk
> > 
> > 
> > Dear Colleagues,
> > 
> > In an effort to break this naming deadlock, and with Massimo and
> > Ian not showing up as yet, I checked the IUCr Dictionary.
> > 
> > “Redundancy“ and “Multiplicity“ are not listed.
>

Re: [ccp4bb] AW: [ccp4bb] AW: [ccp4bb] AW: [EXTERNAL] Re: [ccp4bb] number of frames to get a full dataset?

[Gerard Bricogne]

Dear Herman and David,

 This thread seems inexhaustible :-) .

 On the matter of "measurement" vs. "observation", we seem again to be
in a situation described by the British idiom "half of one and half-a-dozen"
of the other, i.e. distinct but synonymous terms between which a choice is
quite indifferent.

 In the work on STARANISO and the documentation of that work, a
distinction had to be made between the two terms, for which readers are
referred to Ian's carefully crafted material at 

http://staraniso.globalphasing.org/anisotropy_about.html

and 

http://staraniso.globalphasing.org/staraniso_glossary.html

Here, a measurement is a number plucked out of examining the raw data,
namely an integrated intensity obtained by considering the pixel values
around the position in 3D reciprocal space predicted from an indexing
solution. The next step is to determine whether this qualifies as an
observation, in the sense of containing information that a structural model
would be expected to comply with. This determination is carried out by
computing a local average of I/sig(I) through reciprocal space and applying
a cut-off criterion based on a threshold value for that local average. Other
criteria can be considered, and are indeed offered by the program as
alternatives. Measurements complying with this selection criterion are then
called "observations". In this picture, an observation is defined as a
significant measurement. This basic distinction of vocabulary is then
extended to talking about "unmeasured" reflections (for which there weren't
any detector pixels to catch any photons at their predicted position - e.g.
in gaps between detector modules) and "unobserved" reflections (that are
unmeasured but for which the analysis of the I/sig(I) distribution predicts
that they would have been significant, had they been measured - e.g. in
cusps or missing angular ranges, as well as in module gaps etc.). The
display of the latter as blue dots in the STARANISO Reciprocal Lattice
Viewer then gives a vivid picture of the inadequacies of the experimental
protocol used, in failing to catch all the significant diffraction from the
sample.

 This being said, things could very well had been done the other way,
saying that the blindly integrated intensity was an observation, and that
the subsequent analysis was intended to determine whether you had really
measured something significant (i.e. a useful integrated intensity) by
making that observation. We were aware of this ambivalence, but felt that we
had to comply with the boundary condition that what we ended up with, after
conversion to an amplitude, had to be denoted "Fobs" ;-) . If the early
crystallographers had used the notation "Fmeas" for what they considered as
their experimental data, the choice of terminology would definitely have
gone the other way.

 As Graeme said, use the terminology you want, but document exactly what
you mean by it. The two URLs quoted above (especially the second) show that
this suggestion was conscientiously followed by the STARANISO developers.


 With best wishes,

  Gerard,

--
On Fri, Jul 03, 2020 at 10:22:43AM +, Schreuder, Herman /DE wrote:
> Dear David,
> 
> Thank you for your reaction. It has become clear to me that although most 
> people understand what I intended with “measurement”, in practice it is very 
> much in the eye of the beholder. It was suggested in the BB to use 
> observation instead, but I am fairly sure that some people will also have 
> issues with that.
> 
> The advantage of multiplicity/redundancy is that it does not mention what is 
> multiple or redundant and that one can refer to the program documentation for 
> an exact definition. Since most people are happy with the 
> multiplicity/redundancy they grew up with, that is the way it will stay.
> 
> Best regards,
> Herman
> 
> 
> 
> 
> Von: David Waterman 
> Gesendet: Freitag, 3. Juli 2020 10:49
> An: Schreuder, Herman /DE 
> Cc: CCP4BB@jiscmail.ac.uk
> Betreff: Re: [ccp4bb] AW: [ccp4bb] AW: [EXTERNAL] Re: [ccp4bb] number of 
> frames to get a full dataset?
> 
> 
> EXTERNAL : Real sender is dgwater...@gmail.com
> 
> Hi Herman,
> 
> I like the idea of MPR, but I continue to worry about the term "measurement". 
> The intensity associated with a particular reflection is a fit based on a 
> scaling model, and ultimately, depending on your integration software, may be 
> linked to a weighted sum of two raw measurements: the summation and 
> profile-fitted intensities. I think these are the measurements, not the 
> intensity derived during the scaling procedure. Sure, anyone who wants to be 
> even more pedantic than me will point out that these "raw measurements" are 
> also the result of fitting procedures. However, to my eyes, the difference is 
> that we don't consider the profile and summation integrated intensities to 
> change as a result of the procedure that ultimately determines 

Re: [ccp4bb] Quote source inquiry

[Gerard Bricogne]

Dear Harry,

 I think that sharp ice rings (or, better, a powder pattern from silicon
powder) are only part of the solution to the calibration of beam energy, as
there is an interaction with the detector distance. If I recall what I saw
in my now distant days at LURE, a precise energy calibration would be done
using an absorption edge. I can remember Richard Kahn using a Cu metal foil
to lock precisely onto an energy close to the Ytterbium edge he wanted to
use in a MAD experiment. When the beam energy is precisely established by
this diffraction-free method, then a Si powder allows a precise calibration
of detector distance (and location of beam centre). 


 With best wishes,

  Gerard.

--
On Thu, Jul 16, 2020 at 12:25:55PM +0100, Harry Powell - CCP4BB wrote:
> Hi
> 
> Does anyone bother collecting a powder image (e.g. Si powder) these days so 
> they actually have a reference that can be used to check both the wavelength 
> and the beam centre? Or is this considered just something that old folk do?
> 
> Harry
> 
> > On 16 Jul 2020, at 12:19, Gerard DVD Kleywegt  wrote:
> > 
> > There was a case a few years ago (not too many though) where a 1.6 Å 
> > structure had been solved using an incorrect value for the wavelength (~5% 
> > too low, leading to a cell that was slightly too small for its contents to 
> > be comfortable). It was later corrected so we could compare their 
> > validation statistics. Some interesting observations:
> > 
> > - the geometry had been very tightly restrained so that didn't give a clue
> >  about the cell error (WhatCheck only suggested a very small change)
> > 
> > - somewhat surprisingly (I thought) the Ramachandran plot did not improve in
> >  the correct model (0.3% outliers in the wwPDB validation report), and the
> >  sidechain rotamer outliers even got worse (from 1.5 to 2.5 %)
> > 
> > - the map looked surprisingly good for the incorrect cell
> > 
> > - however, RSR-Z told clearly that the map was not good enough for the 
> > claimed
> >  resolution - the model had 24% outliers! (3% in the corrected model which
> >  still only put it at the ~50th percentile)
> > 
> > - another good indicator was the clashscore (went from 44 to 7)
> > 
> > - the original model did not include an Rfree, but the R-value (>0.3 at 1.6Å
> >  resolution) ought to have provided a clue to the crystallographers and
> >  reviewers one would think
> > 
> > It would be interesting to see what would happen if the wavelength would be 
> > set 5% too high.
> > 
> > --Gerard
> > 
> > 
> > 
> > On Thu, 16 Jul 2020, Clemens Vonrhein wrote:
> > 
> >> Hi Robbie,
> >> 
> >> On Wed, Jul 15, 2020 at 07:23:15PM +, Robbie Joosten wrote:
> >>> At the same time if you have a a more relaxed approach to restraints
> >>> than you might find systematic deviations in bond lengths. A test
> >>> for that has been in WHAT_CHECK for decades and it actually works
> >>> surprisingly well to detect cell dimension problems.
> >> 
> >> Indeed.
> >> 
> >>> That said, the problem is uncommon now.
> >> 
> >> Not so sure about that: we all rely on an accurate value of the
> >> energy/wavelength from the instrument/beamline - and if that is off
> >> (for whatever reasons) it will result in incorrect cell dimensions and
> >> a systematic deviation from the various restraints.
> >> 
> >> This would even affect the best experiment done on the best crystal
> >> ... so fairly easy to spot at the refinement stage, especially if such
> >> an energy/wavelength offset is constant over a long period of time on
> >> a given instrument. To spot this at the data collection stage one
> >> would hope that at some point a crystal with very pronounced ice-rings
> >> will be looked at properly (and the fact these are not where we expect
> >> them to should cause some head-scratching).
> >> 
> >> Cheers
> >> 
> >> Clemens
> >> 
> >> 
> >> 
> >> To unsubscribe from the CCP4BB list, click the following link:
> >> https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1
> >> 
> >> This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing 
> >> list hosted by www.jiscmail.ac.uk, terms & conditions are available at 
> >> https://www.jiscmail.ac.uk/policyandsecurity/
> >> 
> > 
> > 
> > Best wishes,
> > 
> > --Gerard
> > 
> > **
> >   Gerard J. Kleywegt
> > 
> >  http://xray.bmc.uu.se/gerard   mailto:ger...@xray.bmc.uu.se
> > **
> >   The opinions in this message are fictional.  Any similarity
> >   to actual opinions, living or dead, is purely coincidental.
> > **
> >   Little known gastromathematical curiosity: let "z" be the
> >   radius and "a" the thickness of a pizza. Then the volume
> >of that pizza is equa

Re: [ccp4bb] autoPROC question

[Gerard Bricogne]

Dear Almudena,

 I am glad that you got some helpful responses by writing to the ccp4bb
about your problem, and would like to thank those who sent them.

 Please note, however, that there is a user support mailing list for
autoPROC, called "proc-deve...@globalphasing.com", where such questions will
always be welcome and will be answered by the developers themselves.


 With best wishes,

  Gerard.

--
On Sat, Nov 07, 2020 at 08:45:39PM +0100, Almudena Ponce Salvatierra wrote:
> Hi Kay, Michal, Guillermo,
> 
> thank you all for your answers.
> 
> @Kay Diederichs  and Michal, indeed I tried
> with the XDS outputs first, since this is what I'm most familiar with.
> However, when I load them in Xtriage to see how the data is going to look
> overall, I see that only I, SIGI are there. See the screenshot attached.
> 
> @Guillermo Montoya  I am trying! :) My images
> are from a Pilatus detector, in cbf format. Is what you sent in this later
> email equivalent to "process -I Directory_1_002 -I Directory_1_003 -I
> Directory_1_004 -I Directory_1_005 -I Directory_1_006 -I Directory_1_007 -I
> Directory_1_008 -I Directory_1_009 -d 0comb -ANO"
> 
> You wrote -*Id* directory/image...cbf but I was not able to run it like
> that... so I used -I... it's running now.
> 
> Thank you very much everyone. Have a nice Saturday evening!
> 
> Best,
> 
> Almu
> 
> El sáb., 7 nov. 2020 a las 20:09, Kay Diederichs (<
> kay.diederi...@uni-konstanz.de>) escribió:
> 
> > Hello Almudena,
> >
> > XDS_ASCII.HKL _has_ all the information. Whether the HKL values of a given
> > record of that file refer to I(+) or I(-) is worked out by the scaling
> > program.
> >
> > HTH,
> > Kay
> >
> > On Sat, 7 Nov 2020 19:07:59 +0100, Almudena Ponce Salvatierra <
> > maps.fa...@gmail.com> wrote:
> >
> > >Hello everyone,
> > >
> > >I am using autoPROC in a series of datasets I referred to in an email a
> > few
> > >days ago.
> > >
> > >I would like to merge them and see if the resulting dataset has enough
> > >anomalous signal as to phase.
> > >
> > >The thing is that, out of the massive output from autoPROC, I fail to find
> > >which files to merge. I am using the command "combine_files -f ... -f ...
> > >-o combined.mtz". But neither aimless_unmerged.mtz or XDS_ASCII.HKL files,
> > >seem to contain any record of I(+)I(-) etc...
> > >
> > >I'll be very thankful for any suggestions.
> > >
> > >Best,
> > >
> > >Almudena
> > >
> > >
> > >
> > >To unsubscribe from the CCP4BB list, click the following link:
> > >https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1
> > >
> > >This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a
> > mailing list hosted by www.jiscmail.ac.uk, terms & conditions are
> > available at https://www.jiscmail.ac.uk/policyandsecurity/
> > >
> >
> > 
> >
> > To unsubscribe from the CCP4BB list, click the following link:
> > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1
> >
> > This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a
> > mailing list hosted by www.jiscmail.ac.uk, terms & conditions are
> > available at https://www.jiscmail.ac.uk/policyandsecurity/
> >
> 
> 
> 
> To unsubscribe from the CCP4BB list, click the following link:
> https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1
> 
> This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing 
> list hosted by www.jiscmail.ac.uk, terms & conditions are available at 
> https://www.jiscmail.ac.uk/policyandsecurity/



To unsubscribe from the CCP4BB list, click the following link:
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This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list 
hosted by www.jiscmail.ac.uk, terms & conditions are available at 
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Re: [ccp4bb] autoPROC question

[Gerard Bricogne]

Dear Almudena,

 Let me give you a bit more guidance regarding the files of interest.

 The main user-oriented output from autoPROC is the "summary.html" file.
Numerous files are linked from within that html file, that are not meant to
be looked at individually with bare hands. This summary documents the steps
followed by autoPROC, and the final section "Finalising output" has all the
information you need as to what files contain what, with links to them so
that you can easily download them without having to inspect directories
yourself.

 It is the final sub-section, annotated "anisotropic", that contains
these links, as well as a printed Table 1. The file you want is called
"staraniso_alldata-unique.mtz". If you just used the XDS_ACII.HKL you would
forfeit the extra treatment by STARANISO. There is a "table1" link to the
contents, as a separate text file, of the box shaded in light green in the
summary file, and a link "xml" with this information in XML form for
harvesting by synchrotron auto-processing pipelines. You will also find a
link "Data_1_autoPROC_STARANISO_all.cif" that directs you to an mmCIF file
containing the final data, ready for deposition into the PDB. Finally, for
good measure, there is link to a full PDF report of the autoPROC results,
called "report_staraniso.pdf".

 I hope this guidance is of some help. The main message is: look at the
summary.html file.

 It has been clear for some time that users expect to be able to use
programs without having to look at the documentation, but it is a relatively
new development that they expect to be able to use the results without
having to look at any output :-) .


 With best wishes,

  Gerard.

--
On Sat, Nov 07, 2020 at 10:06:58PM +, Gerard Bricogne wrote:
> Dear Almudena,
> 
>  I am glad that you got some helpful responses by writing to the ccp4bb
> about your problem, and would like to thank those who sent them.
> 
>  Please note, however, that there is a user support mailing list for
> autoPROC, called "proc-deve...@globalphasing.com", where such questions will
> always be welcome and will be answered by the developers themselves.
> 
> 
>  With best wishes,
> 
>   Gerard.
> 
> --
> On Sat, Nov 07, 2020 at 08:45:39PM +0100, Almudena Ponce Salvatierra wrote:
> > Hi Kay, Michal, Guillermo,
> > 
> > thank you all for your answers.
> > 
> > @Kay Diederichs  and Michal, indeed I tried
> > with the XDS outputs first, since this is what I'm most familiar with.
> > However, when I load them in Xtriage to see how the data is going to look
> > overall, I see that only I, SIGI are there. See the screenshot attached.
> > 
> > @Guillermo Montoya  I am trying! :) My images
> > are from a Pilatus detector, in cbf format. Is what you sent in this later
> > email equivalent to "process -I Directory_1_002 -I Directory_1_003 -I
> > Directory_1_004 -I Directory_1_005 -I Directory_1_006 -I Directory_1_007 -I
> > Directory_1_008 -I Directory_1_009 -d 0comb -ANO"
> > 
> > You wrote -*Id* directory/image...cbf but I was not able to run it like
> > that... so I used -I... it's running now.
> > 
> > Thank you very much everyone. Have a nice Saturday evening!
> > 
> > Best,
> > 
> > Almu
> > 
> > El sáb., 7 nov. 2020 a las 20:09, Kay Diederichs (<
> > kay.diederi...@uni-konstanz.de>) escribió:
> > 
> > > Hello Almudena,
> > >
> > > XDS_ASCII.HKL _has_ all the information. Whether the HKL values of a given
> > > record of that file refer to I(+) or I(-) is worked out by the scaling
> > > program.
> > >
> > > HTH,
> > > Kay
> > >
> > > On Sat, 7 Nov 2020 19:07:59 +0100, Almudena Ponce Salvatierra <
> > > maps.fa...@gmail.com> wrote:
> > >
> > > >Hello everyone,
> > > >
> > > >I am using autoPROC in a series of datasets I referred to in an email a
> > > few
> > > >days ago.
> > > >
> > > >I would like to merge them and see if the resulting dataset has enough
> > > >anomalous signal as to phase.
> > > >
> > > >The thing is that, out of the massive output from autoPROC, I fail to 
> > > >find
> > > >which files to merge. I am using the command "combine_files -f ... -f ...
> > > >-o combined.mtz". But neither aimless_unmerged.mtz or XDS_ASCII.HKL 
> > > >files,
> > > >seem to contain any record of I(+)I(-) etc...
> > > >
> > > >I'll be very thankful for any suggestion

Re: [ccp4bb] No Cl- or S Anomalous Signal

[Gerard Bricogne]

emistry & Molecular Biology
> >> Johns Hopkins Malaria Research Institute
> >> 615 North Wolfe Street, W8708
> >> Baltimore, MD 21205
> >> Office: +1-410-614-4742
> >> Lab:  +1-410-614-4894
> >> Fax:  +1-410-955-2926
> >> http://web.mac.com/bosch_lab/
> >> 
> >> 
> >> 
> >> 
> >> 
> > 
> > 
> > 
> > -- 
> > ***
> > Jacob Pearson Keller
> > Northwestern University
> > Medical Scientist Training Program
> > cel: 773.608.9185
> > email: j-kell...@northwestern.edu
> > ***
> 
> --
> Randy J. Read
> Department of Haematology, University of Cambridge
> Cambridge Institute for Medical Research  Tel: + 44 1223 336500
> Wellcome Trust/MRC Building   Fax: + 44 1223 336827
> Hills RoadE-mail: rj...@cam.ac.uk
> Cambridge CB2 0XY, U.K.   www-structmed.cimr.cam.ac.uk

-- 

 ===
 * *
 * Gerard Bricogne g...@globalphasing.com  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
 * *
 ===

Re: [ccp4bb] should the final model be refined against full datset

[Gerard Bricogne]

Dear Tom,

 I am not sure that I feel happy with your invitation that views on such
crucial matters as these deposition issues be communicated to you off-list.
It would seem much healthier if these views were aired out within the BB. 
Again!, some will say ... but the difference is that there is now a forum
for them, set up by the IUCr, that may eventually turn opinions into some
form of action.

 I am sure that many subscribers to this BB, and not just you as a
member of some committees, would be interested to hear the full variety of
views on the desirable and the feasible in these areas, and to express their
own for everyone to read and discuss.

 Perhaps John Helliwell can elaborate on this and on the newly created
forum.


 With best wishes,
 
  Gerard.

--
On Fri, Oct 14, 2011 at 04:56:20PM -0600, Thomas C. Terwilliger wrote:
> For those who have strong opinions on what data should be deposited...
> 
> The IUCR is just starting a serious discussion of this subject. Two
> committees, the "Data Deposition Working Group", led by John Helliwell,
> and the Commission on Biological Macromolecules (chaired by Xiao-Dong Su)
> are working on this.
> 
> Two key issues are (1) feasibility and importance of deposition of raw
> images and (2) deposition of sufficient information to fully reproduce the
> crystallographic analysis.
> 
> I am on both committees and would be happy to hear your ideas (off-list). 
> I am sure the other members of the committees would welcome your thoughts
> as well.
> 
> -Tom T
> 
> Tom Terwilliger
> terwilli...@lanl.gov
> 
> 
> >> This is a follow up (or a digression) to James comparing test set to
> >> missing reflections.  I also heard this issue mentioned before but was
> >> always too lazy to actually pursue it.
> >>
> >> So.
> >>
> >> The role of the test set is to prevent overfitting.  Let's say I have
> >> the final model and I monitored the Rfree every step of the way and can
> >> conclude that there is no overfitting.  Should I do the final refinement
> >> against complete dataset?
> >>
> >> IMCO, I absolutely should.  The test set reflections contain
> >> information, and the "final" model is actually biased towards the
> >> working set.  Refining using all the data can only improve the accuracy
> >> of the model, if only slightly.
> >>
> >> The second question is practical.  Let's say I want to deposit the
> >> results of the refinement against the full dataset as my final model.
> >> Should I not report the Rfree and instead insert a remark explaining the
> >> situation?  If I report the Rfree prior to the test set removal, it is
> >> certain that every validation tool will report a mismatch.  It does not
> >> seem that the PDB has a mechanism to deal with this.
> >>
> >> Cheers,
> >>
> >> Ed.
> >>
> >>
> >>
> >> --
> >> Oh, suddenly throwing a giraffe into a volcano to make water is crazy?
> >> Julian, King of Lemurs
> >>

-- 

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Re: [ccp4bb] Dennis Ritchie

[Gerard Bricogne]

Dear Miguel,

 Your list of two astounding achievements by Ritchie reminds me of an
old satire of mutual assessment within academia, in cartoon form, showing a
group of cavemen talking intensely and secretively to each other about
another one who is standing anxiously in the distance. One of those in the
group is saying: "OK, so he discovered fire and invented the wheel - but
what has he done since?".


 With best wishes,
 
  Gerard.

--
On Tue, Oct 18, 2011 at 10:58:05AM +0200, Miguel Ortiz Lombardía wrote:
> Hi community,
> 
> I have been waiting for someone more knowledgeable to write about the
> passing away of Dennis Ritchie (8 October) especially after the recent
> obituaries posted in the list. I confess I know little about him, except:
> 
> 1/ He created the C language ( and together with Brian Kernighan wrote
> an extremely useful book about it )
> 2/ He and Ken Thompson were key in the development of something called
> UNIX...
> 
> Undoubtedly, he made an impact in our field.
> 
> 
> -- 
> Miguel
> 
> Architecture et Fonction des Macromolécules Biologiques (UMR6098)
> CNRS, Universités d'Aix-Marseille I & II
> Case 932, 163 Avenue de Luminy, 13288 Marseille cedex 9, France
> Tel: +33(0) 491 82 55 93
> Fax: +33(0) 491 26 67 20
> mailto:miguel.ortiz-lombar...@afmb.univ-mrs.fr
> http://www.afmb.univ-mrs.fr/Miguel-Ortiz-Lombardia

-- 

 =======
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Re: [ccp4bb] Dennis Ritchie

[Gerard Bricogne]

Dear Sabuj,

 Your opening remark made me worried that the facetious "what has he
done since?" might be taken seriously ... . That was not what was intended!
A variant of the joke was about a similar committee in charge of evaluating
God's performance, and coming up with "Sure, he created the Universe, but
what has he done since?". I was certainly not implying that Dennis Ritchie
had slept on his laurels after the two pieces of work Miguel mentioned - I
was only trying to share some light humour about the often over-competitive
and pettily critical system under which we all have to live and operate.


 With best wishes,
 
  Gerard.

--
On Tue, Oct 18, 2011 at 09:36:21AM -0500, Sabuj Pattanayek wrote:
> The silence on this list was deafening.
> 
> > group is saying: "OK, so he discovered fire and invented the wheel - but
> > what has he done since?".
> 
> 1983 Turing Award
> 1990 IEEE Hamming medal
> 1999 National Medal of Technology
> 2011 Japan Prize for Information and Communications (while he was
> still alive I think)
> 
> Even if he hadn't done anything technologically innovative that was
> made public since C and UNIX, his C book (which was the first
> programming book I read in it's entirety) and the foundations of his
> OS have helped countless millions of people. I find it sad that in
> many undergrad computer science curricula, C is no longer being
> taught. If you want to understand how software works under the hood
> you either learn assembly or C.

Re: [ccp4bb] IUCr committees, depositing images

[Gerard Bricogne]

 other half of the story.
>
> From a biological point of view, only borderline cases make "cents" ($+€) 
> to store.
> The experimenter in consultation with a beamline scientist at an SR 
> facility is the best
> small commitee suitable to evaluate what is worth keeping. I am sure that 
> the images
> that are worth storing for a long long time would fit on a few Tb at a 
> reasonable cost.
> Storing everything would make it harder to find something worth improving 
> in the future.
>
> Enrico.
>
>
> On Tue, 18 Oct 2011 17:12:42 +0200, Peter Keller 
>  wrote:
>
>> Dear Enrico,
>>
>> Please don't get me wrong: what you are saying is not incorrect, but it
>> is only half the story.
>>
>> On Tue, 2011-10-18 at 15:13 +0200, Enrico Stura wrote:
>>> With improving techniques, we should always be making progress!
>>
>> Yes, of course!
>>
>>> If we are trying to answer a biological question that is really 
>>> important,
>>> we would be better off
>>> improving the purification, the crystallization, the cryo-conditions
>>
>> You have left X-ray crystallography out of this list. It is a technique
>> like the others, and can also be improved :-)
>>
>> It may be true that the number of crystallographers that are working on
>> improving instrumental methodology and software is small compared to the
>> number working on improving wet-lab techniques, but that number is not
>> zero, and the contribution is significant. The rest of you benefit from
>> that work!
>>
>>> instead of having to rely on
>>> processing old images with new software.
>>>
>>> I have 10 years  worth of images. I have reprocessed very few of them and
>>> never made any
>>> sensational progress using the new software. Poor diffraction is poor
>>> diffraction.
>>
>> Maybe so, but certain types of datasets are useful for methods and
>> software development, even if no new biological insights could be gained
>> by reprocessing them. These datasets are often hard to get hold of in
>> practice, especially when they are in someone's lab on a tape that
>> no-one has a reader for any more.
>>
>> Obtaining protein, growing crystals and collecting new data in such a
>> way that the interesting features of those datasets are reproduced can
>> be much much harder than curating the images would be. This is
>> especially true for software-oriented people like us who don't have
>> regular access to wet-lab facilities.
>>
>>> Money can be better spent buying a wine cellar, storage works for wine.
>>
>> Images have already been lost that ought to have been kept. The
>> questions are: how to select the datasets that are potentially of value,
>> and how to make sure that they don't disappear.
>>
>> Regards,
>> Peter.
>>
>
>
> -- 
> Enrico A. Stura D.Phil. (Oxon) ,Tel: 33 (0)1 69 08 4302 Office
> Room 19, Bat.152,   Tel: 33 (0)1 69 08 9449Lab
> LTMB, SIMOPRO, IBiTec-S, CE Saclay, 91191 Gif-sur-Yvette,   FRANCE
> http://www-dsv.cea.fr/en/institutes/institute-of-biology-and-technology-saclay-ibitec-s/unites-de-recherche/department-of-molecular-engineering-of-proteins-simopro/molecular-toxinology-and-biotechnology-laboratory-ltmb/crystallogenesis-e.-stura
> http://www.chem.gla.ac.uk/protein/mirror/stura/index2.html
> e-mail: est...@cea.fr Fax: 33 (0)1 69 08 90 71

-- 

 ===
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 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
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Re: [ccp4bb] IUCr committees, depositing images

[Gerard Bricogne]

fewer crystal structures than Acta E and would thus be more
> manageable. The overall advantage of the responsibility being with
> Journals as we see it is that it encourages such 'archiving of data
> with literature' across all crystallography related techniques (single
> crystal, SAXS, SANS, Electron crystallography etc) and fields
> (Biology, Chemistry, Materials, Condensed Matter Physics etc) ie not
> just one technique and field, although obviously biology is dear to
> our hearts here in the CCP4bb.
> 
> Yours sincerely,
> John and Tom
> John Helliwell  and Tom Terwilliger
> 
> On Wed, Oct 26, 2011 at 9:21 AM, Frank von Delft
>  wrote:
> > Since when has the cost of any project been limited by the cost of
> > hardware?  Someone has to implement this -- and make a career out of it;
> > thunderingly absent from this thread has been the chorus of volunteers who
> > will write the grant.
> > phx
> >
> >
> > On 25/10/2011 21:10, Herbert J. Bernstein wrote:
> >
> > To be fair to those concerned about cost, a more conservative estimate
> > from the NSF RDLM workshop last summer in Princeton is $1,000 to $3,000
> > per terabyte per year for long term storage allowing for overhead in
> > moderate-sized institutions such as the PDB.  Larger entities, such
> > as Google are able to do it for much lower annual costs in the range of
> > $100 to $300 per terabyte per year.  Indeed, if this becomes a serious
> > effort, one might wish to consider involving the large storage farm
> > businesses such as Google and Amazon.  They might be willing to help
> > support science partially in exchange for eyeballs going to their sites.
> >
> > Regards,
> >H. J. Bernstein
> >
> > At 1:56 PM -0600 10/25/11, James Stroud wrote:
> >
> > On Oct 24, 2011, at 3:56 PM, James Holton wrote:
> >
> > The PDB only gets about 8000 depositions per year
> >
> > Just to put this into dollars. If each dataset is about 17 GB in
> > size, then that's about 14 TB of storage that needs to come online
> > every year to store the raw data for every structure. A two second
> > search reveals that Newegg has a 3GB hitachi for $200. So that's
> > about $1000 / year of storage for the raw data behind PDB deposits.
> >
> > James
> >
> >
> 
> 
> 
> -- 
> Professor John R Helliwell DSc

-- 

 ===
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 * Gerard Bricogne g...@globalphasing.com  *
 * *
 * Global Phasing Ltd. *
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Re: [ccp4bb] IUCr committees, depositing images

[Gerard Bricogne]

n PDB depositions. There seems to be a view that the 
> archiving of this should be the responsibility of the synchrotrons which 
> generated the data. This should be possible for some synchrotrons (e.g. 
> Diamond) where there is pressure in any case from their funders to archive 
> all data generated at the facility. However not all synchrotrons will be able 
> to do this. There is also the issue of data collected at home sources. 
> Presumably it will require a few willing synchrotrons to pioneer this in a 
> coordinated way. Hopefully others will then follow. I don't think we can 
> expect the PDB to archive the 99.96% of the data which did not result in 
> structures.
> 
> 5.  My view is that for data in the PDB the same release rules should apply 
> for the images as for the other data. For other data, the funders of the 
> research might want to define release rules. However, we can make suggestions!
> 
> 6. Looking to the future, there is FEL data coming along, both single 
> molecule and nano-crystals (assuming the FEL delivers for these areas).
> 
> 7. I agree with Gerard B - "as far as I see it, the highest future benefit of 
> having archived raw images will result from being able to reprocess datasets 
> from samples containing multiple lattices" 
> My view is that all crystals are, to a greater or lesser extent, subject to 
> this. We just might not see it easily as the detector resolution or beam 
> divergence is inadequate. Just think we could have several structures (one 
> from each lattice) each with less disorder rather than just one average 
> structure.  Not sure whether Gloria's modulated structures would be as 
> ubiquitous but her argument is along the same lines.
> 
> Regards 
>   Colin
> 
> -Original Message-
> From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Herbert 
> J. Bernstein
> Sent: 26 October 2011 18:55
> To: ccp4bb
> Subject: Re: [ccp4bb] IUCr committees, depositing images
> 
> Dear Colleagues,
> 
>Gerard strikes a very useful note in pleading for a "can-do"
> approach.  Part of going from "can-do" to "actually-done"
> is to make realistic estimates of the costs of "doing" and
> then to adjust plans appropriately to do what can be afforded
> now and to work towards doing as much of what remains undone
> as has sufficient benefit to justify the costs.
> 
>We appear to be in a fortunate situation in which some
> portion of the raw data behind a signficant portion of the
> studies released in the PDB could probably be retained for some
> significant period of time and be made available for further
> analysis.  It would seem wise to explore these possibilities
> and try to optimize the approaches used -- e.g. to consider
> moves towards well documented formats, and retention of critical
> metadata with such data to help in future analysis.
> 
>Please do not let the perfect be the enemy of the good.
> 
>    Regards,
>  Herbert
> 
> =
>   Herbert J. Bernstein, Professor of Computer Science
> Dowling College, Kramer Science Center, KSC 121
>  Idle Hour Blvd, Oakdale, NY, 11769
> 
>   +1-631-244-3035
>   y...@dowling.edu
> =
> 
> On Wed, 26 Oct 2011, Gerard Bricogne wrote:
> 
> > Dear John and colleagues,
> >
> > There seem to be a set a centrifugal forces at play within this thread
> > that are distracting us from a sensible path of concrete action by throwing
> > decoys in every conceivable direction, e.g.
> >
> > * "Pilatus detectors spew out such a volume of data that we can't
> > possibly archive it all" - does that mean that because the 5th generation of
> > Dectris detectors will be able to write one billion images a second and
> > catch every scattered photon individually, we should not try and archive
> > more information than is given by the current merged structure factor data?
> > That seems a complete failure of reasoning to me: there must be a sensible
> > form of raw data archiving that would stand between those two extremes and
> > would retain much more information that the current merged data but would
> > step back from the enormous degree of oversampling of the raw diffraction
> > pattern that the Pilatus and its successors are capable of.
> >
> > * "It is all going to cost an awful lot of money, therefore we need a
> > team of grant writers to raise its hand and volunteer to apply for resources
> > from one or more funding agencies" - there

Re: [ccp4bb] IUCr committees, depositing images

[Gerard Bricogne]

ove were
actually discussed, even if some of them might have been only partially
recorded. I do dream about these matters at night, but I don't think that I
hallucinate (yet). 


 I hope, finally, that this goes some way towards providing the
clarification you wanted.


 With best wishes,
 
  Gerard.

--
On Wed, Oct 26, 2011 at 03:10:21PM +, John Helliwell wrote:
> Dear Gerard,
> Thankyou for your CCP4bb detailed message of today, 
> 
> But I have to come off line re :-
> The IUCr Forum already has an outline of a feasibility study that would cost 
> only a small amount of
> joined-up thinking and book-keeping around already stored information, so let 
> us not use the inaccessibility of federal or EC funding as a scarecrow to 
> justify not even trying what is proposed there.
> 
> and especially:-
> already stored information
> 
> Where exactly is this existing store to which you refer?
> 
> 
> The PDB is out it seems to take on this role for the MX community so it 
> leaves us with convincing the Journals. I have started with IUCr Journals and 
> have submitted a Business Plan, already a month ago. 
> It has not instantly led to 'lets do it' but I remain hopeful that that 
> doesn't mean 'No'.
> 
> I copy in Tom and Brian.
> 
> In anticipation of your clarification.
> 
> Thankyou.
> Yours sincerely,
> John
> Prof John R Helliwell DSc 
=======

(Below, the message John was referring to in his request for clarification)

--
Date: Wed, 26 Oct 2011 15:29:32 +0100
From: Gerard Bricogne 
Subject: Re: [ccp4bb] IUCr committees, depositing images
To: CCP4BB@JISCMAIL.AC.UK

Dear John and colleagues,

 There seem to be a set a centrifugal forces at play within this thread
that are distracting us from a sensible path of concrete action by throwing
decoys in every conceivable direction, e.g.

 * "Pilatus detectors spew out such a volume of data that we can't
possibly archive it all" - does that mean that because the 5th generation of
Dectris detectors will be able to write one billion images a second and
catch every scattered photon individually, we should not try and archive
more information than is given by the current merged structure factor data?
That seems a complete failure of reasoning to me: there must be a sensible
form of raw data archiving that would stand between those two extremes and
would retain much more information that the current merged data but would
step back from the enormous degree of oversampling of the raw diffraction
pattern that the Pilatus and its successors are capable of.

 * "It is all going to cost an awful lot of money, therefore we need a
team of grant writers to raise its hand and volunteer to apply for resources
from one or more funding agencies" - there again there is an avoidance of
the feasible by invocation of the impossible. The IUCr Forum already has an
outline of a feasibility study that would cost only a small amount of
joined-up thinking and book-keeping around already stored information, so
let us not use the inaccessibility of federal or EC funding as a scarecrow
to justify not even trying what is proposed there. And the idea that someone
needs to decide to stake his/her career on this undertaking seems totally
overblown.

 Several people have already pointed out that the sets of images that
would need to be archived would be a very small subset of the bulk of
datasets that are being held on the storage systems of synchrotron sources.
What needs to be done, as already described, is to be able to refer to those
few datasets that gave rise to the integrated data against which deposited
structures were refined (or, in some cases, solved by experimental phasing),
to give them special status in terms of making them visible and accessible
on-line at the same time as the pdb entry itself (rather than after the
statutory 2-5 years that would apply to all the rest, probably in a more
off-line form), and to maintain that accessibility "for ever", with a link
from the pdb entry and perhaps from the associated publication. It seems
unlikely that this would involve the mobilisation of such large resources as
to require either a human sacrifice (of the poor person whose life would be
staked on this gamble) or writing a grant application, with the indefinite
postponement of action and the loss of motivation this would imply.

 Coming back to the more technical issue of bloated datasets, it is a
scientific problem that must be amenable to rational analysis to decide on a
sensible form of compression of overly-verbose sets of thin-sliced, perhaps
low-exposure images that would already retain a large fraction, if not all,
of the extra information on which we would wish future improved versions of
processing programs to cu

Re: [ccp4bb] raw data deposition

[Gerard Bricogne]

Dear Ed,

 I am really puzzled by this initiative. It assumes that there is a
pre-formed "collective opinion" out there, independent from and unaffected
by the exchanges of views that have taken place on this BB, that would be
worth more than the conclusions we might reach by pursuing these exchanges.

 The thread you are obviously deciding to dissociate yourself from was
initiated in response to a suggestion that views on this topic would
usefully be aired publicly on this BB rather than posted off-list to Tom
Terwilliger, who immediately agreed that this was a good idea and has been
very supportive of this discussion.

 Shouldn't we continue to try and put our heads together to reach a
consensus, rather than collect opinions that may be little more than prior
prejudices?

 What shall we gain by such a vote? I may be misunderstanding what you
have in mind, of course :-) .


 With best wishes,
 
  Gerard.

--
On Thu, Oct 27, 2011 at 12:08:24PM -0400, Ed Pozharski wrote:
> I am curious as to what the collective opinion on the raw data
> deposition actually is across the cross-section of the macromolecular
> crystallography community subscribed to the bb.  So, if you have a
> second and a formed opinion on the idea of the depositions of the raw
> data, please vote here
> 
> http://tinyurl.com/3qlwwsh
> 
> I'll post the results as soon as they look settled.
> 
> Cheers,
> 
> Ed.
> 
> -- 
> "Hurry up before we all come back to our senses!"
>Julian, King of Lemurs

-- 

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Re: [ccp4bb] raw data deposition

[Gerard Bricogne]

Dear Jacob,

 I agree, of course, with the goal of giving everyone a voice, but
knowing that 40% of the voters find storing images a waste of time falls
short of knowing why they think so and taking their arguments into account.
Disagreeing without saying why when a topic is being actively discussed is a
position that does not contribute anything very constructive. 

 I think there should be an extra category of answer that would be
"I don't care", so that people who have no opinion do not get confused with
those who have an articulate position against the proposal, and wh should
then articulate it!


 With best wishes,
 
  Gerard.

--
On Thu, Oct 27, 2011 at 11:30:20AM -0500, Jacob Keller wrote:
> One thing that the poll is useful for is something I find surprising:
> ~40% when I checked found storing images a waste of time. So, I guess
> this might be useful for finding the "silent [significant] minority."
> Why not have those folks chime in about why they think this is
> useless, even to store images of solved datasets?
> 
> JPK
> 
> On Thu, Oct 27, 2011 at 11:25 AM, Gerard Bricogne
>  wrote:
> > Dear Ed,
> >
> >     I am really puzzled by this initiative. It assumes that there is a
> > pre-formed "collective opinion" out there, independent from and unaffected
> > by the exchanges of views that have taken place on this BB, that would be
> > worth more than the conclusions we might reach by pursuing these exchanges.
> >
> >     The thread you are obviously deciding to dissociate yourself from was
> > initiated in response to a suggestion that views on this topic would
> > usefully be aired publicly on this BB rather than posted off-list to Tom
> > Terwilliger, who immediately agreed that this was a good idea and has been
> > very supportive of this discussion.
> >
> >     Shouldn't we continue to try and put our heads together to reach a
> > consensus, rather than collect opinions that may be little more than prior
> > prejudices?
> >
> >     What shall we gain by such a vote? I may be misunderstanding what you
> > have in mind, of course :-) .
> >
> >
> >     With best wishes,
> >
> >          Gerard.
> >
> > --
> > On Thu, Oct 27, 2011 at 12:08:24PM -0400, Ed Pozharski wrote:
> >> I am curious as to what the collective opinion on the raw data
> >> deposition actually is across the cross-section of the macromolecular
> >> crystallography community subscribed to the bb.  So, if you have a
> >> second and a formed opinion on the idea of the depositions of the raw
> >> data, please vote here
> >>
> >> http://tinyurl.com/3qlwwsh
> >>
> >> I'll post the results as soon as they look settled.
> >>
> >> Cheers,
> >>
> >> Ed.
> >>
> >> --
> >> "Hurry up before we all come back to our senses!"
> >>                            Julian, King of Lemurs
> >
> > --
> >
> >     ===
> >     *                                                             *
> >     * Gerard Bricogne                     g...@globalphasing.com  *
> >     *                                                             *
> >     * Global Phasing Ltd.                                         *
> >     * Sheraton House, Castle Park         Tel: +44-(0)1223-353033 *
> >     * Cambridge CB3 0AX, UK               Fax: +44-(0)1223-366889 *
> >     *                                                             *
> >     ===
> >
> 
> 
> 
> -- 
> ***
> Jacob Pearson Keller
> Northwestern University
> Medical Scientist Training Program
> email: j-kell...@northwestern.edu
> ***

Re: [ccp4bb] raw data deposition

[Gerard Bricogne]

Dear Nat,

 You are making an excellent point, that I would like to supplement with
another drawn from an intermediate stage between making compulsory the
deposition of coordinates (to which you are referring) and the discussion we
are having right now about moving towards the deposition of diffraction
images - namely, the deposition of "structure factor" data.

 At first that idea seemed to many to be just as far-fetched as the
current one is seen by many. I can remember an impassioned e-mail to this BB
by Gerard Kleywegt with subject line "SOS: save our structure factors!",
pleading the case for that deposition to be made cmpulsory so as to be make 
it possible to have as objective a picture as possible of the quality of the
electron density on which the model was based; and he went on to produce the
Electron Density Server, the usefulness of which few would now dispute.
There are probably few instances in which the EDS could be proven to have
led to "significant new biological insights", but it is undeniable that it
must have provided very useful means of checking deposited structures to see
whether there might be questionable bits in crucial regions, whereas
previously one would have had to believe indiscriminately everything that
was modelled.

 This structure factor deposition also led to the possibility of
large-scale testing of new developments in refinement algorithms which
played a huge role in helping improvements in those to be throroughly
evaluated, and the programs to be made robust. This led in turn to being
able to see more detail or more corrections in old pdb entries via the EDS,
culminating in such initiatives as PDB-redo that, if not revolutionising the
biological information content of the pdb, has certainly helped make its
contents much more assessable. Through the effect on the improvement of
refinement programs, it can be said that the greatest beneficiaries of the
deposition of structure factors yesterday are not so much the people who
deposited the associated structures at the time, but everyone who refines
structures today and will do so tomorrow with the much improved programs it
has helped produce.

 We are simply today at the logical next step, i.e. depositing the
images that the structure factors came from. For many reasons that have been
described by many people, images often contain much more information about
the reliability (or otherwise) of the structure factors derived from them (I
have repeatedly mentioned the corruption by reflexions from parasitic
lattices). Such images will not only provide the foodstuff for new
developments aimed at dealing better with the problem: once those
developments have taken place, more reliable data will be obtainable from
them, that may frequently clean up dubious features of the previous maps or
bring into question certain parts of the previous models. I think that
Adrian's rather dismissive comment that developers can get the job done from
a few scraps of bad images gleaned from colleagues in distress is simply a
sign of a lack of experience in developing software. 

 We should not, therefore, be too blinkered and ask only "What will it
do for my structure if I deposit my images", but instead ask "What will
depositing my images do to improve the processing and refinement programs of
tomorrow" (I am not trying to sound like JFK here ...). The answer is: an
awful lot! These improvements will then help everybody, including the
sceptical depositor in question in his or her next tough project; but as
usual they will be taken for granted by those who thought that depositing
images was a waste of time ... .

 I hope this elicits more comments from doubters and detractors: their
voices and arguments should certainly be heard.


 With best wishes,
 
  Gerard.

--
On Thu, Oct 27, 2011 at 02:11:28PM -0700, Nat Echols wrote:
> On Thu, Oct 27, 2011 at 1:47 PM, Adrian Goldman
> wrote:
> 
> > 1) this is not a matter of science, but science (internal) policy, and so
> > the majority actually SHOULD count.
> >
> 
> It's worth keeping in mind that there was once strong opposition to the
> current rules on PDB deposition - the best example I could find is here:
> 
> http://www.nature.com/nsmb/journal/v5/n6/pdf/nsb0698-407.pdf
> 
> Notably, nearly a third of scientists polled thought they should be allowed
> to publish without releasing coordinates.  If this had been a majority,
> should the journal editors have meekly submitted and allowed the old policy
> of 1-year holds to continue?  Admittedly, the issue of archiving raw images
> is not the same, since they are of much less use to the community, but it's
> a good example of why some opinions should be ignored.
> 
> -Nat

-- 

 =======

Re: [ccp4bb] raw data deposition

[Gerard Bricogne]

Dear Adrian,

 I too follow Voltaire, and your point of view nicely illustrates the
diversity of outlook and priorities between practitioners of our arcane art.

 I can only say that I have seen many cases where structural detail only
obtainable through hard work in phasing and/or refinement has produced
conclusions that had a significant impact on the ambient biological story,
and that this hard work would not have been possible if no one had cared
about continuing to develop ever better methods and software.


 With best wishes,
 
  Gerard.

--
On Fri, Oct 28, 2011 at 01:40:11AM +0300, Adrian Goldman wrote:
> Ok. This is my last post before I go to bed. Look at the opportunity cost of 
> this discussion alone - bright minds who should be solving structures or 
> developing algorithms - anything! Debating this. 
> 
> However - as someone else remarked will (a) anyone care about > 90% of the 
> structures in 50 years?  
> 
> And (b) even if they do, is this continual improvement even worthwhile?  I  
> am always depressed at how little a model changes from an initial build to 
> the final one, even when the rfree drops from 35 to 23. All that work! - and 
> my biological interpretation would have been almost the same at the beginning 
> as at the end. 
> 
> The structures aren't important in themselves. It's the story they tell. So 
> to me this is an effort to fix what ain't broke. 
> 
> Adrian
> 
> Sent from my iPhone
> 
> On 28 Oct 2011, at 01:15, Michel Fodje  wrote:
> 
> > Every dataset costs money to produce. Is it more cost effective to expect 
> > that those wishing to use the data repeat the expenditures by repeating the 
> > experiments?  To exaggerate the point, imagine a world without published 
> > research articles, would it be more expensive to do science or less? We 
> > should not simply dismiss an idea just because we think today that "640K is 
> > more memory than anyone will ever need"
> > 
> > 
> >> On Oct 27, 2011, at 3:47 PM, Adrian Goldman wrote:
> >> 2) I agree with Susan.  In a time of limited funding, is this the most 
> >> important use of money?
> > 

-- 

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Re: [ccp4bb] raw data deposition

[Gerard Bricogne]

Dear Fred,

 Frankly, with respect, this sounds to me like fanciful and rather
non-sensical paranoia. The time frame for public disclosure of all SR data
has been quoted at 5 years, or something of that order. If someone has been
unable to solve a structure 5 years after having collected data on it, then
it does make perfect sense that he/she be "rescued" in one way or another.
Any responsible scientist in that situation would have called for specialist
help long before then, and having failed to do so would indicate a loss of
interest in the project anyway.

 This is again the type of argument that strays away from a serious
question by throwing decoys around the place. Of course such views must be
heard, but so should the counter-arguments of those who disagree with them. 


 With best wishes,
 
  Gerard.

--
On Fri, Oct 28, 2011 at 10:42:25AM +0200, Vellieux Frederic wrote:
> D Bonsor wrote:
>> and allow someone else to have ago at solving the structure.
>>   
>
> I'd be careful there if there was a motion to try to implement a policy at 
> SR sources (for academic research projects) to make it compulsory to 
> publically release all data frames after a period (1 year ? 2 years ? 4 
> years) during which you are supposed to solve the structures you have 
> collected the data for, so that others can have a go at it (and solve the 
> structures "for you"):
>
> you may find yourself for example in between grants and need to spend all 
> of your time looking for funding for a couple of years, with little or no 
> staff working with you. With the trend we see of ever diminishing 
> resources, this would mean that the very large and well funded labs and 
> groups would solve their own structures, and solve those of smaller groups 
> as well (and publish the latter). This would then mean (after a while) the 
> concentration of macromolecular crystallography to only the "lucky few" who 
> have managed to secure large grants and will therefore go-on securing such 
> grants. You could call that "evolution" I suppose.
>
> We are already in a situation where the crystallographers who solved the 
> structures are not necessarily authors on the publications reporting the 
> structures... so is it time to go back to home sources (X-ray generators) 
> for data collection ?
>
> Fred.

-- 

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Re: [ccp4bb] raw data deposition

[Gerard Bricogne]

Dear Remy,

 You are right, and I was about to send a message confessing that I had
been rash in my response to Fred's. Another person e-mailed me off-list to
point out that sometimes a structure can be quickly solved, but that doing
all the rest of the work involved in wrapping that structure into a good
biological story for publication can take a very long time, and that it
would be wrong for a SR source's forced disclosure policy to start imposing
deadlines on that process. I entirely agree with both of you and admit that
I reacted too quickly and with insufficient thought to Fred's message.

 However, as you point out yourself, this issue is related to a
different question (SR sources' disclosure policy towards all data collected
on their beamlines) from the original one that started this thread
(deposition of raw images with the pdb entries they led to). The two topics
became entangled through the idea of prototyping an approach to the latter
by tweaking the storage and access features involved in the former. 

 Many thanks to you and to the other correspondent for picking up and
correcting my error. This however leaves the main topic of this thread
untouched.


 With best wishes,
 
  Gerard.

--
On Fri, Oct 28, 2011 at 01:38:29PM +0200, Remy Loris wrote:
> Dear Gerard,
>
> I cannot agree. Last year my group published a paper in Cell which 
> contained a structure for which the native data were collected at a 
> synchrotron around 1997. Various reasons contributed to the long lag period 
> for solving this structure, but basically it all came down to money needed 
> to do the work. Equally I am sure there are other cases for which a first 
> good native data set is a breakthrough you wish to protect rather than hand 
> it out to anyone who might potentially scoop you after you have put lots of 
> money and effort into the project.
>
> Therefore: Images corresponding to structures I deposit in the PDB: No 
> problem. That is what we do with processed data as well. But images of 
> unsolved structures, I don't see why that should be enforced or done 
> automatically by synchrotrons. Nobody deposits processed data without an 
> accompanying structure either.
>
> I do agree that one could be given the option to deposit interesting data 
> with which he/se will not continue for whatever reason. But this should be 
> optional, and a clear consensus should emerge within the community as how 
> the original producers of the data have to be acknowledged if these data 
> are used and the results published by another team, especially if the use 
> of that particular dataset is crucial for the publication.
>
> Remy Loris
> Vrije Universiteit Brussel and VIB
>
>
> Op 28/10/2011 11:54, Gerard Bricogne schreef:
>> Dear Fred,
>>
>>   Frankly, with respect, this sounds to me like fanciful and rather
>> non-sensical paranoia. The time frame for public disclosure of all SR data
>> has been quoted at 5 years, or something of that order. If someone has 
>> been
>> unable to solve a structure 5 years after having collected data on it, 
>> then
>> it does make perfect sense that he/she be "rescued" in one way or another.
>> Any responsible scientist in that situation would have called for 
>> specialist
>> help long before then, and having failed to do so would indicate a loss of
>> interest in the project anyway.
>>
>>   This is again the type of argument that strays away from a serious
>> question by throwing decoys around the place. Of course such views must be
>> heard, but so should the counter-arguments of those who disagree with 
>> them.
>>
>>
>>   With best wishes,
>>
>>Gerard.
>>
>> --
>> On Fri, Oct 28, 2011 at 10:42:25AM +0200, Vellieux Frederic wrote:
>>> D Bonsor wrote:
>>>> and allow someone else to have ago at solving the structure.
>>>>
>>> I'd be careful there if there was a motion to try to implement a policy 
>>> at
>>> SR sources (for academic research projects) to make it compulsory to
>>> publically release all data frames after a period (1 year ? 2 years ? 4
>>> years) during which you are supposed to solve the structures you have
>>> collected the data for, so that others can have a go at it (and solve the
>>> structures "for you"):
>>>
>>> you may find yourself for example in between grants and need to spend all
>>> of your time looking for funding for a couple of years, with little or no
>>> staff working with you. With the trend we see of ever diminishing
>>> resources, this would mean that the very large and well f

Re: [ccp4bb] raw data deposition

[Gerard Bricogne]

Dear Jacob,

 See the paper by J. Wang cited at the end of Francis Reyes's message
under this thread yesterday: it is a case of exactly what you are talking
about.


 With best wishes,
 
  Gerard.

--
On Fri, Oct 28, 2011 at 10:05:44AM -0500, Jacob Keller wrote:
> What about a case in which two investigators have differences about
> what cutoff to apply to the data, for example, A thinks that Rsym of
> 50 should be used regardless of I/sig, and B thinks that I/sig of 2
> and Rpim should be used. Usually A would cut off the data at a lower
> resolution than B, especially with high multiplicity, so B would love
> to have the images to see what extra info could be gleaned from a
> higher-res cutoff. Or the converse, A is skeptical of B's cutoff, and
> wants to see whether the data according to A's cutoff justify B's
> conclusion. Don't these types of things happen a lot, and wouldn't
> images be helpful for this?
> 
> JPK

-- 

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 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
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Re: [ccp4bb] raw data deposition (off-list)

[Gerard Bricogne]

Dear Petr,

 I agree that we need tools to validate processing methods, but these
tools will not come from pure thought alone: they will need vast amount of
raw data with a full range of problematic features so that the ideas of new
approaches and the algorithms to implement them can be developed and tested.
The main tools for validating methods are data!

 Also, validation is nice, but catching a problem by means of a
validation procedure does not mean being able to correct it. It is only by
retaining the original data that one can be certain not to have lost any of
the information the experiment gave through an inappropriate processing
method.

 In other words, quality of outcome does not materialise without a huge
amount of challenging data to guide and test the underlying developments,
i.e. without a large amount of storage - so I don't think the two can be
decoupled in the way you suggest.

 As I and many have said often, once you have used those stored raw data
to improve processing methods, you can go back to those same raw data and
reprocess them, to get better reduced data and hence better structural
results from them: that would not happen if you hadn't stored them in the
first place.


 With best wishes,
 
  Gerard.

--
On Fri, Oct 28, 2011 at 08:33:53AM +0200, Petr Kolenko wrote:
> Dear colleagues,
> 
> my opinion is that we should develop methods or approaches to validate
> !processing! of raw data. If this is possible. We have many validation
> tools for structure refinement, but no tool to validate data
> processing. In case we have this tools, there is no need to deposit
> diffraction images (2-5GB instead of 10 MB). I think.
> Of course, how to validate this? This might be topic for a new
> discussion. I am sure, that in the very beginning of crystallography,
> there were no tools to validate the structures as well. I am also sure
> that some opinions may arise today. (Online server, where one can
> upload the images with log files from processing?)
> We should concentrate more on quality of our outcome, than on storage
> of these data.
> 
> Petr
> 
> 
> 2011/10/28 Katherine Sippel :
> > Generally during these rigorous bb debates I prefer to stay silent and
> > absorb all the information possible so that I can make an informed decision
> > later on. I fear that I am compelled to contribute in this instance. In
> > regards to the "does this make a difference in the biological interpretation
> > stage" issue, I can state that it does. In my comparatively miniscule career
> > I have run into this issue three times. The first two address Adrian's
> > point...
> >
> >> And (b) even if they do, is this continual improvement even worthwhile?  I
> >>  am always depressed at how little a model changes from an initial build to
> >> the final one, even when the rfree drops from 35 to 23. All that work! - 
> >> and
> >> my biological interpretation would have been almost the same at the
> >> beginning as at the end.
> >
> >
> > In one instance I adopted an orphaned structure and ran it through a
> > slightly more advanced refinement protocol (on the same structure factors)
> > and ended up with a completely different story than the one I started with
> > [1]. Another researcher in my grad lab identified mis-oriented catalytic
> > residues in an existing structure from EDS server maps which affects the
> > biochemistry of the catalytic mechanism [2].
> >
> > In another case I decided that I would reprocess some images that I had
> > originally indexed and scaled in my "Ooo buttons clicky clicky" stage of
> > learning crystallography and the improved structure factors revealed a
> > alternate conformations for both a critical loop and ligand orientation [3].
> >
> > And this was all in the last 4 years. So I would posit that the answer is
> > yes there are significant biological insights to be had with the capacity to
> > reassess data in any form.
> >
> > Katherine
> >
> > [1] J Phys Chem Lett. 2010 Oct 7;1(19):2898-2902
> > [2] Acta Crystallogr D Biol Crystallogr. 2009 Mar;65(Pt 3):294-6.
> > [3] Manuscript in progress
> >
> > 
> > Katherine Sippel, PhD
> > Postdoctoral Associate
> > Baylor College of Medicine
> >
> 
> 
> 
> -- 
> Petr Kolenko
> kole...@imc.cas.cz
> http://kolda.webz.cz

-- 

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Re: [ccp4bb] To archive or not to archive, that's the question!

[Gerard Bricogne]

Be! RCSB and PDBj will have to 
> acquire storage as well.) Moreover, disks have to be housed in a building 
> (not free!), with cooling, security measures, security staff, maintenance 
> staff, electricity (substantial cost!), rental of a 1-10 Gb/s connection, 
> etc. All hardware has a life-cycle of three years (barring failures) and 
> then needs to be replaced (at lower cost, but still not free).
>
> - if the data is going to be stored centrally, how will it get there? Using 
> ftp will probably not be feasible.
>
> - if it is not stored centrally, how will long-term data availability be 
> enforced? (Otherwise I could have my data on a public server until my paper 
> comes out in print, and then remove it.)
>
> - what level of annotation will be required? There is no point in having 
> zillions of files lying around if you don't know which 
> structure/crystal/sample they belong to, at what wavelength they were 
> recorded, if they were used in refinement or not, etc.
>
> - an issue that has not been raised yet, I think: who is going to validate 
> that the images actually correspond to the structure factor amplitudes or 
> intensities that were used in the refinement? This means that the data will 
> have to be indexed, integrated, scaled, merged, etc. and finally compared 
> to the deposited Fobs or Iobs. This will have to be done for *10,000 data 
> sets a year*... And I can already imagine the arguments that will follow 
> between depositors and "re-processors" about what software to use, what 
> resolution cut-off, what outlier-rejection criteria, etc. How will 
> conflicts and discrepancies be resolved? This could well end up taking a 
> day of working time per data set, i.e. with 200 working days per year, one 
> would need 50 *new* staff for this task alone. For comparison: worldwide, 
> there is currently a *total* of ~25 annotators working for the wwPDB 
> partners...
>
> Not many of you know that (about 10 years ago) I spent probably an entire 
> year of my life sorting out the mess that was the PDB structure factor 
> files pre-EDS... We were apparently the first people to ever look at the 
> tens of thousands of structure factor files and try to use all of them to 
> calculate maps for the EDS server. (If there were others who attempted this 
> before us, they had probably run away screaming.) This went well for many 
> files, but there were many, many files that had problems. There were dozens 
> of different kinds of issues: non-CIF files, CIF files with wrong headers, 
> Is instead of Fs, Fcalc instead of Fobs, all "h" equal to 0, 
> non-space-separated columns, etc. For a list, see: 
> http://eds.bmc.uu.se/eds/eds_help.html#PROBLEMS
>
> Anyway, my point is that simply having images without annotation and 
> without reprocessing is like having a crystallographic kitchen sink (or bit 
> bucket) which will turn out to be 50% useless when the day comes that 
> somebody wants to do archive-wide analysis/reprocessing/rerefinement etc. 
> And if the point is to "catch cheaters" (which in my opinion is one of the 
> weakest, least-fundable arguments for storage), then the whole operation is 
> in fact pointless without reprocessing by a "third party" at deposition 
> time.
>
> ---
>
> (3) Funding.
>
> This is one issue we can't really debate - ultimately, it is the funding 
> agencies who have to be convinced that the cost/benefit ratio is low 
> enough. The community will somehow have to come up with a stable, long-term 
> funding model. The outcome of (2) should enable one to estimate the initial 
> investment cost plus the variable cost per year. Funding could be done in 
> different ways:
>
> - centrally - e.g., a big application for funding from NIH or EU
>
> - by charging depositors (just like they are charged Open Access charges, 
> which can often be reclaimed from the funding agencies) - would you be 
> willing to pay, say, 5000 USD per dataset to secure "perpetual" storage?
>
> - by charging users (i.e., Gerard Bricogne :-) - just kidding!
>
> Of course, if the consensus is to go for decentralised storage and a 
> DOI-like identifier system, there will be no need for a central archive, 
> and the identifiers could be captured upon deposition in the PDB. (We could 
> also check once a week if the files still exist where they are supposed to 
> be.)
>
> ---
>
> (4) Location.
>
> If the consensus is to have decentralised storage, the solution is quite 
> simple and very cheap in terms of "centralised" cost - wwPDB can capture 
> DOI-like identifiers upon deposition and make them searchable.
>
> If central storage is needed, then there has to be an

Re: [ccp4bb] To archive or not to archive, that's the question!

[Gerard Bricogne]

ata sets could be accommodated.
>>> Please do email me off list with this information if you prefer but
>>> within the CCP4bb is also good.
>>>
>>
>> Dear John,
>>
>> I'm pretty sure that there exists no consistent policy to provide an 
>> "institutional repository" for deposition of scientific data at German 
>> universities or Max-Planck institutes or Helmholtz institutions, at least 
>> I never heard of something like this. More specifically, our University of 
>> Konstanz certainly does not have the infrastructure to provide this.
>>
>> I don't think that Germany is the only country which is the exception to 
>> any rule of availability of "institutional repository" . Rather, I'm 
>> almost amazed that British and American institutions seem to support this.
>>
>> Thus I suggest to not focus exclusively on official institutional 
>> repositories, but to explore alternatives: distributed filestores like 
>> Google's BigTable, Bittorrent or others might be just as suitable - check 
>> out http://en.wikipedia.org/wiki/Distributed_data_store. I guess that any 
>> crystallographic lab could easily sacrifice/donate a TB of storage for the 
>> purposes of this project in 2011 (and maybe 2 TB in 2012, 3 in 2013, ...), 
>> but clearly the level of work to set this up should be kept as low as 
>> possible (a bittorrent daemon seems simple enough).
>>
>> Just my 2 cents,
>>
>> Kay
>>
>
> P please don't print this e-mail unless you really need to
> Anastassis (Tassos) Perrakis, Principal Investigator / Staff Member
> Department of Biochemistry (B8)
> Netherlands Cancer Institute,
> Dept. B8, 1066 CX Amsterdam, The Netherlands
> Tel: +31 20 512 1951 Fax: +31 20 512 1954 Mobile / SMS: +31 6 28 597791
>

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Re: [ccp4bb] To archive or not to archive, that's the question!

[Gerard Bricogne]

s to evaluate that, and how? The question is 
> not that we could do it. We could do it, but wouldn't it advance science 
> far more if we would spend the time and money in new projects rather than 
> evaluation, administration, etc?

 There are many ways of advancing science, and perhaps every
specialist's views of this question are biased towards his/her own. We agree
that archiving of images without all the context within which they were
recorded would be futile. Gerard K raised the issue of all the manual work
one might have to contemplate if the PDB staff were to manually check that
the images do belong where they are supposed to. I think this is a false
problem. We need to get the synchrotron beamlines to do a better, more
consistent, more standardised job of keeping interconnected records linking
user projects to sample decriptors to image sets to processing results. The
pharma industry do that successfully: when they file the contents of their
hard disk after a synchrotron trip, they do not rely on extra staff to check
that the image do go with the targets and the ligands, as if they had just
received them in a package dellivered in the morning post: consistency is
built into their book-keeping system, that includes the relevant segment of
that process that gets executed at the synchrotron. 

--
> Be honest: How many of you have really, and completely, reanalysed your own 
> data, that you have deposited 10 years ago, with the latest software? What 
> changes did you find? Did you have to re-write your former discussions in 
> the publications? Do you think that the changes justify the efforts and 
> costs of worldwide archiving of all data?

 OK, good question, but the answer might not be what you expect. It is
the possibility of going back to raw data if some "auditing" of an old
result is required that is the most important. It is like an insurance
policy: would you ask people "How many of you have made calls on your
policies recently" and use the smallness of the proportion of YESs as an
argument for not getting one?

--
> Well, for all cases there are always (and have been mentioned in earlier 
> emails) single cases where these things matter or mattered. But does this 
> really justify all the future efforts and costs to archive the 
> exponentially (!) increasing amount of data? Do we need all this effort for 
> better statistics tables? Do you believe the standard lab biologist will 
> look into all the images at all? Is the effort just for us 
> crystallographers? As long as just a few dozen users would re-analyse the 
> data it is not worth it.

 I think that here again you are calling upon the argument of the
"market" for structural results among "standard lab biologist(s)". This is
important of course, and laudible efforts are being made by the PDB to make
its contents more aprroachable and digestible by that audience. That is a
different question, though, from that of continuing to improving the
standards of quality of crystallographic results produced by the community,
and in particular of the software tools produced by methods developers. On
that side of the divide, different criteria apply from those that matter the
most in the "consumer market" of lab biologists. The shift to
maximum-likelihood methods in phasing and refinement, for instance, did not
take place in response to popular demand from that mass market, if I recall
- and yet it made a qualitative difference to the quality and quantity of
the results they now have at their disposal.

--
> I like question marks, and maybe someone can give me an argument for 
> archiving images. At the moment I would vote for not archiving.

 I think that the two examples I gave at the beginning should begin to
answer your "why" question: because each reduced dataset might have fallen
victim to unanticipated shortcomings of the software (and underlying
assumptions) available at the time. I will be hard to convince that one can
anticipate the absence of unanticipated pitfalls of this kind ;-) . 


 With best wishes,
 
  Gerard.



> With best regards,
>
> Martin
>
>
> P.S. For the next-gen sequencing data, they have found a new way of 
> transferring the data, called VAN (the newbies might google for it) in 
> analogy to the old-fashioned and slow LAN and WLAN. Maybe we will also 
> adopt to this when archiving our data?
>
> -- 
> Priv. Doz. Dr. Martin Kollmar
>
> Max-Planck-Institute for Biophysical Chemistry
> Group Systems Biology of Motor Proteins
> Department NMR-based Structural Biology
> Am Fassberg 11
> 37077 Goettingen
> Deutschland
>
> Tel.: +49 551 2012260 / 2235
> Fax.: +49 551 2012202
>
> www.motorprotein.de (Homepage)
> www.cymobase.org (Database of Cytoskeletal and Motor Proteins)
> www.diar

Re: [ccp4bb] To archive or not to archive, that's the question!

[Gerard Bricogne]

Dear Martin,

 First of all I would like to say that I regret having made my "remark
500" and apologise if you read it as a personal one - I just saw it as an
example of a dataset it might have been useful to revisit if data had been
available in any form. I am sure that there are many skeletons in many
cupboards, including my own :-) .

 Otherwise, as the discussion does seem to refocus on the very initial
proposal in gestation within the IUCr's DDDWG, i.e. voluntary involvement of
depositors and of synchrotrons, so that questions of logistics and cost
could be answered in the light of empirical evidence, your "Why" question is
the only one unanswered by this proposal, it seems.

 In this respect I wonder how you view the two examples I gave in my
reply to your previous message, namely the "corner effects" problem and the
re-development of methods for collating data from numerous small, poorly
diffracting crystals as was done in the recent solution of GPCR structures.
There remains the example I cited from the beginning, namely the integration
of images displaying several overlapping lattices. 


 With best wishes,
 
  Gerard.

--
On Mon, Oct 31, 2011 at 05:01:38PM +0100, Martin Kollmar wrote:
> The point is that science is not collecting stamps. Therefore the first 
> question should always be "Why". If you start with "What" the discussion 
> immediately switches to technical issues like how many TB, PB etc. $/EUR, 
> manpower. And all the intense discussion will blow out by one single "Why". 
> Nothing is for free. But if it would help science and mankind, nobody would 
> hesitate to spend millions of $/EUR.
>
> Supporting software development / software developers is a different 
> question. If this were the  first question that someone would have asked 
> the answer would have never been "archiving all datasets worldwide / 
> deposited structures", but how could we, the community, build up a resource 
> with different kind of problems (e.g. space groups, twinning, overlapping 
> lattices, etc.).
>
> I still didn't got an answer for "Why".
>
> Best regards,
> Martin
>
>
>
> Am 31.10.2011 16:18, schrieb Oganesyan, Vaheh:
>> I was hesitant to add my opinion so far because I'm used more to listen 
>> this forum rather than tell others what I think.
>> "Why" and "what" to deposit are absolutely interconnected. Once you decide 
>> why you want to do it, then you will probably know what will be the best 
>> format and /vice versa/.
>> Whether this deposition of raw images will or will not help in future 
>> understanding the biology better I'm not sure.
>> But to store those difficult datasets to help the future software 
>> development sounds really farfetched. This assumes that in the future 
>> crystallographers will never grow crystals that will deliver difficult 
>> datasets. If that is the case and in 10-20-30 years next generation will 
>> be growing much better crystals then they don't need such a software 
>> development.
>> If that is not the case, and once in a while (or more often) they will be 
>> getting something out of ordinary then software developers will take them 
>> and develop whatever they need to develop to consider such cases.
>> Am I missing a point of discussion here?
>> Regards,
>>  Vaheh
>> -Original Message-
>> From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of 
>> Robert Esnouf
>> Sent: Monday, October 31, 2011 10:31 AM
>> To: CCP4BB@JISCMAIL.AC.UK
>> Subject: Re: [ccp4bb] To archive or not to archive, that's the question!
>> Dear All,
>> As someone who recently left crystallography for sequencing, I
>> should modify Tassos's point...
>> "A full data-set is a few terabytes, but post-processing
>> reduces it to sub-Gb size."
>> My experience from HiSeqs is that this "full" here means the
>> base calls - equivalent to the unmerged HKLs - hardly raw
>> data. NGS (short-read) sequencing is an imaging technique and
>> the images are more like >100TB for a 15-day run on a single
>> flow cell. The raw base calls are about 5TB. The compressed,
>> mapped data (BAM file, for a human genome, 30x coverage) is
>> about 120GB. It is only a variant call file (VCF, difference
>> from a stated human reference genome) that is sub-Gb and these
>> files are - unsurprisingly - unsuited to detailed statistical
>> analysis. Also $1k is a not yet an economic cost...
>> The DNA information capacity in a single human body dwarfs the
>> entire world disk capacity, so storing DNA is a no brainer
>> here. Sequencing groups are making very hard-nosed economic
>> decisions about what to store - indeed it is a source of
>> research in itself - but the scale of the problem is very much
>> bigger.
>> My tuppence ha'penny is that depositing "raw" images along
>> with everything else in the PDB is a nice idea but would have
>> little impact on science (human/animal/plant health or
>> understanding of biology).
>> 1) If confined to structures in the PDB, t

Re: [ccp4bb] Archiving Images for PDB Depositions

[Gerard Bricogne]

 only the
>>>> specific issue of whether to archive, at least as a start, images
>>>> corresponding to PDB-deposited structures. I believe there could be a
>>>> real consensus about the low cost and usefulness of this degree of
>>>> archiving, but the discussion keeps swinging around to all levels of
>>>> archiving, obfuscating who's for what and for what reason. What about
>>>> this level, alone? All of the accompanying info is already entered
>>>> into the PDB, so there would be no additional costs on that score.
>>>> There could just be a simple link, added to the "download files"
>>>> pulldown, which could say "go to image archive," or something along
>>>> those lines. Images would be pre-zipped, maybe even tarred, and people
>>>> could just download from there. What's so bad?
>>>>
>>>> The benefits are that sometimes there are structures in which
>>>> resolution cutoffs might be unreasonable, or perhaps there is some
>>>> potential radiation damage in the later frames that might be
>>>> deleterious to interpretations, or perhaps there are ugly features in
>>>> the images which are invisible or obscure in the statistics.
>>>>
>>>> In any case, it seems to me that this step would be pretty painless,
>>>> as it is merely an extension of the current system--just add a link to
>>>> the pulldown menu!
>>>>
>>>> Best Regards,
>>>>
>>>> Jacob Keller
>>>>
>>>> -- 
>>>> ***
>>>> Jacob Pearson Keller
>>>> Northwestern University
>>>> Medical Scientist Training Program
>>>> email: j-kell...@northwestern.edu
>>>> ***
>>>>
>
> P please don't print this e-mail unless you really need to
> Anastassis (Tassos) Perrakis, Principal Investigator / Staff Member
> Department of Biochemistry (B8)
> Netherlands Cancer Institute,
> Dept. B8, 1066 CX Amsterdam, The Netherlands
> Tel: +31 20 512 1951 Fax: +31 20 512 1954 Mobile / SMS: +31 6 28 597791

-- 

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Re: [ccp4bb] : Re: [ccp4bb] unusual bond lengths in PRODRG cif file

[Gerard Bricogne]

t; some were very large (> 10 s.d. from mean).
> >
> >  The Mogul program (http://www.ccdc.cam.ac.uk/products/csd_system/mogul/) 
> > can be used to analyse the geometry of any feature in a 3D ligand model 
> > against data in the Cambridge Structural Database and is available to 
> > anyone who has access to the Cambridge Structural Database System. The 
> > GRADE dictionary generation software from Global Phasing uses Mogul 
> > information behind the scenes to generate bond and bond angle restraints. 
> > In addition ligand validation and restraint correction using Mogul will 
> > become available via COOT before too long. Finally you might like to know 
> > we are working with the PDB so that the geometry of ligand models can be 
> > validated on submission.
> >
> >  Regards
> >         John
> >
> > Dr John W. Liebeschuetz
> > Research & Applications Manager
> > Cambridge Crystallographic Data Centre
> > 12 Union Rd., Cambridge CB2 1EZ, UK
> > T:  +44-(0)1223-762532
> > F:  +44-(0)1223-336033
> >
> >
> >
> > LEGAL NOTICE
> > Unless expressly stated otherwise, information contained in this
> > message is confidential. If this message is not intended for you,
> > please inform postmas...@ccdc.cam.ac.uk and delete the message.
> > The Cambridge Crystallographic Data Centre is a company Limited
> > by Guarantee and a Registered Charity.
> > Registered in England No. 2155347 Registered Charity No. 800579
> > Registered office 12 Union Road, Cambridge CB2 1EZ.
> 
> 
> 
> -- 
> Dr Stephen Graham
> 1851 Research Fellow
> Cambridge Institute for Medical Research
> Wellcome Trust/MRC Building
> Addenbrooke's Hospital, Hills Road
> Cambridge, CB2 0XY, UK
> Phone: +44 1223 762 638

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Re: [ccp4bb] MAD

[Gerard Bricogne]

cture of core streptavidin determined from multiwavelength
> >>> anomalous diffraction of synchrotron radiation.
> >>> PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
> >>> AMERICA, 86(7):2190–2194, APR 1989.
> >>> 
> >>> On the other hand, David and Lilo Templeton continued to use the term
> >>> "anomalous dispersion" for at least another decade, describing their
> >>> diffraction experiments exploring polarization effects and other
> >>> characteristics of near-edge X-ray scattering by elements all over the
> >>> periodic table.
> >>> 
> >>>   Ethan
> >>> 
> >>> 
> >>>> Cheers
> >>>> 
> >>>> -- Ian
> >>>> 
> >>>> On 18 January 2012 18:23, Phil Jeffrey  wrote:
> >>>>> Can I be dogmatic about this ?
> >>>>> 
> >>>>> Multiwavelength anomalous diffraction from Hendrickson (1991) Science 
> >>>>> Vol.
> >>>>> 254 no. 5028 pp. 51-58
> >>>>> 
> >>>>> Multiwavelength anomalous diffraction (MAD) from the CCP4 proceedings
> >>>>> http://www.ccp4.ac.uk/courses/proceedings/1997/j_smith/main.html
> >>>>> 
> >>>>> Multi-wavelength anomalous-diffraction (MAD) from Terwilliger Acta 
> >>>>> Cryst.
> >>>>> (1994). D50, 11-16
> >>>>> 
> >>>>> etc.
> >>>>> 
> >>>>> 
> >>>>> I don't see where the problem lies:
> >>>>> 
> >>>>> a SAD experiment is a single wavelength experiment where you are using 
> >>>>> the
> >>>>> anomalous/dispersive signals for phasing
> >>>>> 
> >>>>> a MAD experiment is a multiple wavelength version of SAD.  Hopefully one
> >>>>> picks an appropriate range of wavelengths for whatever complex case one 
> >>>>> has.
> >>>>> 
> >>>>> One can have SAD and MAD datasets that exploit anomalous/dispersive 
> >>>>> signals
> >>>>> from multiple difference sources.  This after all is one of the things 
> >>>>> that
> >>>>> SHARP is particularly good at accommodating.
> >>>>> 
> >>>>> If you're not using the anomalous/dispersive signals for phasing, you're
> >>>>> collecting native data.  After all C,N,O,S etc all have a small 
> >>>>> anomalous
> >>>>> signal at all wavelengths, and metalloproteins usually have even larger
> >>>>> signals so the mere presence of a theoretical d" difference does not 
> >>>>> make it
> >>>>> a SAD dataset.  ALL datasets contain some anomalous/dispersive signals, 
> >>>>> most
> >>>>> of the time way down in the noise.
> >>>>> 
> >>>>> Phil Jeffrey
> >>>>> Princeton
> >>>>> 
> >>>>> 
> >>>>> 
> >>>>> On 1/18/12 12:48 PM, Francis E Reyes wrote:
> >>>>>> 
> >>>>>> 
> >>>>>> Using the terms 'MAD' and 'SAD' have always been confusing to me when
> >>>>>> considering more complex phasing cases.  What happens if you have 
> >>>>>> intrinsic
> >>>>>> Zn's, collect a 3wvl experiment and then derivatize it with SeMet or a 
> >>>>>> heavy
> >>>>>> atom?  Or the MAD+native scenario (SHARP) ?
> >>>>>> 
> >>>>>> Instead of using MAD/SAD nomenclature I favor explicitly stating 
> >>>>>> whether
> >>>>>> dispersive/anomalous/isomorphous differences (and what heavy atoms for 
> >>>>>> each
> >>>>>> ) were used in phasing.   Aren't analyzing the differences 
> >>>>>> (independent of
> >>>>>> source) the important bit anyway?
> >>>>>> 
> >>>>>> 
> >>>>>> F
> >>>>>> 
> >>>>>> 
> >>>>>> -
> >>>>>> Francis E. Reyes M.Sc.
> >>>>>> 215 UCB
> >>>>>> University of Colorado at Boulder
> >>>> 

-- 

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 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
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Re: [ccp4bb] synchrotron X-ray picture

[Gerard Bricogne]

Dear Patrick,

 One such image I can remember was that of the first beam at ESRF. If
you Google for "ESRF first beam", asking for Images, the first one you get
(top left corner) is rather similar. The original one was, I think, more
dramatic than that (or perhaps I was more impressionable). It was an iconic
picture that was used on the front pages of many journals and newsletters at
the time. If someone finds it, I wouldn't mind knowing where to get a copy
of it as well.


 Best of luck!
 
Gerard.

--
On Wed, Feb 01, 2012 at 01:43:19PM -0500, Patrick Loll wrote:
> Hi all,
> 
> I have a vague memory of having a picture in someone's presentation once, 
> showing a smoking hot X-ray beam emerging from the beam pipe in a hutch at a 
> synchrotron. I think the picture might have been a double exposure, with a 
> long exposure that captured air ionization superimposed on a normal photo (or 
> some similar contrivance).
> 
> In any case, can anyone point to or provide such a picture? I'm preparing a 
> seminar, and I want to lend artistic verisimilitude to an otherwise bald and 
> unconvincing narrative...
> 
> Thanks in advance, 
> 
> Pat
> 
> ---
> Patrick J. Loll, Ph. D.  
> Professor of Biochemistry & Molecular Biology
> Director, Biochemistry Graduate Program
> Drexel University College of Medicine
> Room 10-102 New College Building
> 245 N. 15th St., Mailstop 497
> Philadelphia, PA  19102-1192  USA
> 
> (215) 762-7706
> pat.l...@drexelmed.edu

-- 

 =======
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 * Gerard Bricogne g...@globalphasing.com  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
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Re: [ccp4bb] Sad News

[Gerard Bricogne]

Dear Smita,

 For me, your story mostly illustrates the grave dangers of wanting to
own a BMW while still in high school ... ;-) . 


 With best wishes,
 
  Gerard.

--
On Tue, Feb 28, 2012 at 09:02:42AM -0600, Smita Mohanty wrote:
> Yes, this is of course a scam.  My husband was almost duped by someone
> who wrote in the name of a close friend saying that he got mugged in
> Europe and to send money to return to USA. My husband of course was
> ready to send for his colleague but just gave a call to his friend to
> make this not a scam.  Of course, it was a scam.  
> 
> Only last night we saved ourselves from another scam.  I think it is
> good share with the group.  My son (in high school) found a 2005 BMW X5
> on an internet site.  The car's blue book price is $26,000 but the
> asking price by the seller is $2775.  Sounds too good to be true.   But
> when my son (who dreams to own a BMW) contacted the owner (Amanda
> Stone), she replied him immediately saying her son died two months back
> in an automobile accident hit by a drunk driver while riding his
> fiancee's car.  She simply wants to sell the car so that someone else
> can use it and she is not interested in making money.  She said that she
> has a deal with e-bay and that the car will be shipped by e-bay to the
> buyer once the buyer pays the price that will be hold by e-bay.  The
> buyer has 5 days to check the car out and if decides not to buy, the car
> will be shipped back to e-bay at seller's cost and buyer gets back his
> money.  She sent an invoice that was from e-bay with e-bay logo and
> exactly looking genuine.
> 
> She sent car pictures and Vin and my husband checked the car out with
> car fax.  She wanted the money to be sent to a e-bay financial expert
> through moneygram although she sent name and address of an e-bay expert.
>  That is when my husband called up e-bay just to make sure before he
> send the moneygram out.  That is when e-bay told him this is a scam and
> that e-bay never asks for moneygram.  That all transactions are done on
> e-bay site only and that e-bay does not get any contract like the one we
> had.  E-bay told us that their logo has/can be copied to make an invoice
> appears to have come from them.  Of course, we went all communications
> and invoice to e-bay.  We lost only $35 for car fax.
> 
> Lesson: we need to be aware of any advertisements on internet or
> unsolicited e-mails.  Here is a site to read about different scams-
> 
> http://www.fbi.gov/scams-safety/be_crime_smart 
> 
> Thanks,
> 
> Smita 
> 
> >>> Vellieux Frederic  2/28/2012 7:01 AM >>>
> From: regnicat@, reply to: regniica@...
> 
> Somehow I don't believe someone in such a situation would write to 
> ccp4bb instead of calling the family back home. Using Skype since there
> 
> is apparently internet access !
> 
> And I rather view with my mind's eye someone sitting in an internet
> cafe 
> in (say) Lagos, or the Paris suburbs or Kingston or...
> 
> Fred
> 
> Catherine Regni wrote:
> > I'm writing this with tears in my eyes,my family and I came over here
> 
> > to Madrid,Spain for a short vacation. unfortunately,we were  mugged
> at 
> > the park of the hotel where we stayed,all cash and credit card were 
> > stolen off us but luckily for us we still have our passports with
> us.
> >
> >  We've been to the Embassy and the Police here but they're not
> helping 
> > issues at all and our flight leaves in few hours from now but we're 
> > having problems settling the hotel bills and the hotel manager won't
> 
> > let us leave until we settle the bills. Well I really need your 
> > financial assistance..Please, Let me know if you can help us out? Am
> 
> > freaked out at the Moment.
> >
> > Catherine Regni..
> >
> > Catherine Regni, Ph.D.
> >

[ccp4bb] Announcing a Web Server for the Grade ligand restraints generator.

[Gerard Bricogne]

Dear all,

   The generation of reliable restraints for novel small-molecule
ligands in macromolecular complexes is of great importance for both ligand
placement into density maps and subsequent refinement. This has led us to
develop Grade, a ligand restraint generator whose main source of restraint
information is the Cambridge Structural Database (CSD) of small-molecule
crystal structures, queried using the MOGUL program developed by the CCDC.
Where small-molecule information is lacking, Grade uses quantum chemical
procedures to obtain the restraint values.

   Grade was released to academic users as part of the BUSTER package in
July 2011 and has proved popular. However, a problem for numerous academic
users has been that, in order to get the best restraints from Grade, a CSD
system licence is necessary to make use of MOGUL. Although many institutions
already have CSD site licences, and otherwise licences are available at a
reasonable cost, this has prevented the use of Grade by small groups and
occasional users.

   To provide easy access to Grade, the CCDC has kindly agreed that we
can provide a public Web server that includes the use of MOGUL in its
invocation of Grade. The first version of the server is now available, free
of charge, at

   http://grade.globalphasing.org

   We hope this server will prove useful to academic users. We will be
very grateful for any feedback you might be able to provide about this
server, so that we can keep improving it to meet the needs of the community.
Please send us your feedback and comments at 

 buster-deve...@globalphasing.com

rather than write to a specific developer.


   With best wishes,

   The Global Phasing developers: Gerard Bricogne, Claus Flensburg,
   Peter Keller, Wlodek Paciorek, Andrew Sharff, Oliver Smart,
   Clemens Vonrhein and Thomas Womack.

Re: [ccp4bb] one datum many data? [was Re: [ccp4bb] very informative - Trends in Data Fabrication]

[Gerard Bricogne]

Dear Paul,

 May I join the mostly silent chorus of Greek/Latin-aware grumps who
wince when seeing "data" treated as singular when it is plural. Related
instances are

 * a phenomenon (singular) vs. several phenomena (plural),
 
 * a criterion (singular) vs. several criteria (plural)
 
and many more.

 And then there is the infamous mix-up between "principal" (adjective)
and "principle" (noun, as in Principle of Least Action, or Peter's
Principle) giving rise to the favourite hero, the "Principle Investigator".

 This phenomena is now so widespread that perhaps compliance with
ancient Greek or Latin morphology is no longer a relevant criteria ;-) . 


 With best wishes,
 
  Gerard.

--
On Sun, Apr 01, 2012 at 01:05:10PM +0100, Paul Emsley wrote:
> The PDBe page for 3k78 says:
>
> "The experimental data has been deposited"
>
> the data cif file says:
>
> "data is under question"
>
> Grump.
>
> Is it to late to refer to data as if there were more than one of them?
>
> Anyway, the data mtz file is here if you want to refine with it:
>
> http://lmb.bioch.ox.ac.uk/emsley/data/r3k78sf.mtz
>
> Paul.

-- 

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Re: [ccp4bb] one datum many data? [was Re: [ccp4bb] very informative - Trends in Data Fabrication]

[Gerard Bricogne]

On Sun, Apr 01, 2012 at 01:18:15PM -0400, David Schuller wrote:
> On 04/01/12 10:18, Gerard Bricogne wrote:
>> Dear Paul,
>>
>>   May I join the mostly silent chorus of Greek/Latin-aware grumps who
>> wince when seeing "data" treated as singular when it is plural.
> When it are plural?

 Good nit-picking :-) . In my mind the quotes around "data" would have
had the same effect as writing 'the word "data"', and referring to that word
by the 'it'. So there is only one word, while its grammatical number is
plural. 


> At any rate, I heard a Nobel laureate use it incorrectly just two days ago.

 We shouldn't learn to write by imitating Nobel laureates, then.


 With best wishes,
 
  Gerard.

> -- 
> ===
> All Things Serve the Beam
> ===
>David J. Schuller
>modern man in a post-modern world
>MacCHESS, Cornell University
>schul...@cornell.edu

Re: [ccp4bb] one datum many data? [was Re: [ccp4bb] very informative - Trends in Data Fabrication]

[Gerard Bricogne]

Dear Manfred,

 I understand your surprise and indignation, but for the sake of
fairness you might also remember that I argued rather insistently at the end
of last year in favour of the deposition of raw diffraction images, which is
the crux of this problem.


 With best wishes,
 
  Gerard.

--
On Mon, Apr 02, 2012 at 10:47:26AM +0200, Manfred S. Weiss wrote:
> Dear all,
>
> I find this discussion most amazing. Here, we are dealing with the most
> serious issue
> that happened to Macromolecular Crystallography since the Alabama case,
> and the
> whole discussion is centered around singular and plural and Greek and
> Latin words
> and what not.
>
> In psychology such phenomenon is referred to as displacement activity.
>
> If you are interested, here is the MacMillon definition of it:
>
> http://www.macmillandictionary.com/dictionary/british/displacement-activity
>
> Cheers,
>
> Manfred
>
>
> On 01.04.2012 19:35, Gerard Bricogne wrote:
>> On Sun, Apr 01, 2012 at 01:18:15PM -0400, David Schuller wrote:
>>> On 04/01/12 10:18, Gerard Bricogne wrote:
>>>> Dear Paul,
>>>>
>>>>May I join the mostly silent chorus of Greek/Latin-aware grumps 
>>>> who
>>>> wince when seeing "data" treated as singular when it is plural.
>>> When it are plural?
>>   Good nit-picking :-) . In my mind the quotes around "data" would 
>> have
>> had the same effect as writing 'the word "data"', and referring to that 
>> word
>> by the 'it'. So there is only one word, while its grammatical number is
>> plural.
>>
>>
>>> At any rate, I heard a Nobel laureate use it incorrectly just two days 
>>> ago.
>>   We shouldn't learn to write by imitating Nobel laureates, then.
>>
>>
>>   With best wishes,
>>
>>Gerard.
>>
>>> --
>>> ===
>>> All Things Serve the Beam
>>> ===
>>> David J. Schuller
>>> modern man in a post-modern world
>>> MacCHESS, Cornell University
>>> schul...@cornell.edu
>
> --
> Dr. Manfred. S. Weiss
> Helmholtz-Zentrum Berlin für Materialien und Energie
> Macromolecular Crystallography (HZB-MX)
> Albert-Einstein-Str. 15
> D-12489 Berlin
> GERMANY
> Fon:   +49-30-806213149
> Fax:   +49-30-806214975
> Web:   http://www.helmholtz-berlin.de/bessy-mx
> Email: mswe...@helmholtz-berlin.de
>
>
> 
>
> Helmholtz-Zentrum Berlin für Materialien und Energie GmbH
>
> Mitglied der Hermann von Helmholtz-Gemeinschaft Deutscher Forschungszentren 
> e.V.
>
> Aufsichtsrat: Vorsitzender Prof. Dr. Dr. h.c. mult. Joachim Treusch, stv. 
> Vorsitzende Dr. Beatrix Vierkorn-Rudolph
> Geschäftsführerin: Prof. Dr. Anke Rita Kaysser-Pyzalla
>
> Sitz Berlin, AG Charlottenburg, 89 HRB 5583
>
> Postadresse:
> Hahn-Meitner-Platz 1
> D-14109 Berlin
>
> http://www.helmholtz-berlin.de

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 * *
 ===

Re: [ccp4bb] Requested: Three-Day Data Fabrication Workshop

[Gerard Bricogne]

Dear James,

On Mon, Apr 02, 2012 at 08:39:41AM -0700, James Kiefer wrote:
> Dear Jacob,
> 
> With all due respect, you have left out a key component to successful
> data fabrication in the modern age: software.  It is quite obtuse not
> to have allocated at least one day of the workshop for practical
> applications of Photoshop to diffraction image generation and at least
> a passing coverage of whether or not Adobe Lightroom and
> crystallographic presets therein will be sufficiently capable of
> muddling the RCSB staff analysis of data feasibility checking.
> 
> I would very much like to see Gerard Bricogne present a keynote
> lecture entitled something like, "The R-Fake Parameter: A Maximum
> Likelihood Modulus to Define a Minimum Acceptable Data Drift
> Coefficient for Use in the Fabrication of Credibly Artificial
> Diffraction Data."


 Wait a minute ... I have indeed been trying to understand what types of
random processes would best model errors in actual data, but that is in
order to produce better likelihood functions to refine against raw data, not
to better fake errors in fabricated data ;-) - although of course ... . 

 Your suggested title is very good! I will work on a talk, even if the
Workshop never happens.


 With best wishes,
 
  Gerard.

--
> I also believe that we are perhaps full of hubris as a
> crystallographic community, because an entire field of faked
> structural data has existed long before crystallographers even
> considered manufacturing their data.  Specifically,  the molecular
> modeling community has already surpassed us in their thinking on the
> subject.  While we idly discuss how to properly generate false data,
> they have had the foresight to abandon ALL data...and even the
> starting coordinates in crystal structures - be they real or
> fictitious - and publish volumes of papers entirely unencumbered by
> reality or plausibility.  My hat is off to them.
> 
> Best regards,
> Jim
> 
> 
> 
> On Mon, Apr 2, 2012 at 8:15 AM, Jacob Keller
>  wrote:
> > Dear CCP4BB,
> >
> > due to increasing demand, it seems we should put together a workshop on data
> > fabrication, covering the various important topics (chaired by JHo):
> >
> > --Images: the future of fabrication? How long can we rely on database
> > Luddism?
> > --Ways out: how to leave a trail of "accidental" data mix-ups
> > --Publish large or small? Cost-benefit analyses of impact factor vs. risk of
> > being discovered
> > --Pushing the envelope: how significant is two [sic] significant
> > --Crossing discipline boundaries: are data fabrication procedures universal?
> > --Build a better "hofkristallrat"-trap: utilization of rhetorical bombast
> > and indignation in reply letters
> >
> > --Break-out support-session with survivors: comforting words on careers
> > after the fall
> >
> > --Session on the inextricably-related topic of grammatical pedantry, to be
> > followed by a soccer (football?) match Greeks Vs. Latins
> >
> > Ample funding will be available from big pharma and other industry sectors
> >
> > Please submit further topics to the CCP4BB list
> >
> > JPK
> >
> > ps I can't believe no one mentioned the loathsome Latino-Greek "multimer" in
> > the recent curmudgeonry postings.
> >
> >
> > ***
> > Jacob Pearson Keller
> > Northwestern University
> > Medical Scientist Training Program
> > email: j-kell...@northwestern.edu
> > ***
> 
> 
> 
> -- 
> 
> James Kiefer, Ph.D.
> Structural Biology
> Genentech, Inc.
> 1 DNA Way,  Mailstop 27
> South San Francisco, CA 94080-4990

-- 

 ===
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 * *
 * Global Phasing Ltd. *
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Re: [ccp4bb] Disorder or poor phases?

[Gerard Bricogne]

Dear Dale,

 There is perhaps a third factor in the progress you were able to make,
namely the improvement in the refinement programs. Your first results were
probably obtained with a least-squares-based program, while the more recent
would have come from maximum-likelihood-based ones. The difference lies in
the quality of the phase information produced from the model through
comparison of Fo and Fc, with much greater bias-correction capabilities in
the ML approach. Here, it removed the bias towards some regions being absent
in the model, and made them no longer be absent in the maps. So it is a
question of the quality of the phase information.


 With best wishes,
 
  Gerard.

--
On Tue, Apr 10, 2012 at 12:00:28PM -0700, Dale Tronrud wrote:
>The phases do have effects all over the unit cell but that does not
> prevent them from constructively and destructively interfering with one
> another in particular locations.  Some years ago I refined a model of
> the bacteriochlorophyll containing protein to a 1.9 A data set when the
> sequence of that protein was unknown.  This is primarily a beta sheet
> protein and a number of the loops between the strands were disordered.
> Later the amino acid sequence was determined and I finished the refinement
> after building in these corrections.  The same data set was used, but
> a number of the loops had become "ordered".  While the earlier model
> (3BCL) had 357 amino acids the final model (4BCL) had 366.
> 
>These nine amino acids didn't become ordered over the intervening
> years.  They were just as ordered when I was building w/o a sequence,
> it is just that I couldn't see how to build them based on the map's
> appearance.
> 
>One possibility is that the density for these residues was weak
> and the noise (that was uniform over the entire map) obliterated their
> signal where it only obscured the stronger density.  Another possibility
> is that the better model had a better match of the low resolution F's
> and less intense ripples radiating from the surface of the molecule,
> resulting in things "sticking out" being less affected.
> 
>Whatever the details, the density for these amino acids were too
> weak to model with the poorer model phases and became buildable with
> better phases.  The fact that they could not be seen in the early map
> was not an indication that they were "disordered".
> 
>The first six amino acids of this protein have never been seen in
> any map, including the 1.3 A resolution model 3EOJ (which by all rights
> should have been called 5BCL ;-) ).  These residues appear to be truly
> disordered.  Going back to 3BCL - The map for this model is missing
> density for a number of residues of which we know some are disordered
> and some simply unmodelable because of the low quality of the phases.
> I don't know of a way, looking at that map alone, of deciding which
> is which.  Because of this observation I don't believe it is supportable
> to say "I don't see density for these atoms therefore they must be
> disordered."  Additional evidence is required.
> 
> Dale Tronrud
> 
> 
> 
> On 04/10/12 08:38, Tim Gruene wrote:
> > Dear Francis,
> > 
> > the phases calculated from the model affect the whole unit cell hence it
> > is more likely this is real(-space, local) disorder rather than poor
> > phases.
> > 
> > Regards,
> > Tim
> > 
> > P.S.: The author should not look at an 2fofc-map but a
> > sigma-A-weighted map to reduce model bias.
> > 
> > On 04/10/12 17:22, Francis E Reyes wrote:
> >> Hi all,
> > 
> >> Assume that the diffraction resolution is low (say 3.0A or worse)
> >> and the model (a high resolution homologue, from 2A xray data is 
> >> available) was docked into experimental phases (say 4A or worse)
> >> and extended to the 3.0A data using refinement (the high resolution
> >> model as a source of restraints). There are some conformational
> >> differences between the high resolution model and the target
> >> crystal.
> > 
> >> The author observes that in the 2fofc map at 3A, most of the model 
> >> shows reasonable density, but for a stretch of backbone the
> >> density is weak.
> > 
> >> Is the weakness of the density in this region because of disorder
> >> or bad model phases?
> > 
> > 
> >> Would love people's thoughts on this one,
> > 
> >> F
> > 
> > 
> >> - Francis E. Reyes
> >> M.Sc. 215 UCB University of Colorado at Boulder
> > 

Re: [ccp4bb] Off-topic: Supplying PDB file to reviewers

[Gerard Bricogne]

Dear Jeremy,

 Thank you for the attached cartoon, most warmly welcome by all those in
need of a "displacement activity" in this gruesomely cold and rainy month of
April.

 Oh those terrible French! I know them, I am one of them ;-) .
 
 I found the Wikipedia entry on the subject quite entertaining: see
 
  http://en.wikipedia.org/wiki/Discovery_of_Neptune

The conclusions in the "Later analysis" section will arouse suspicions that
it may have been written by a French author - however the graph given in the
previous ("Aftermath") section may be of interest, and speak for itself, in
our current likelihood-aware and (rightly) validation-obsessed frame of mind.

 Back to serious things after this culpable diversion ... . 


 With best wishes,
 
  Gerard.

--
On Thu, Apr 26, 2012 at 02:10:56PM +0900, Jeremy Tame wrote:
> The problem is it is not the PI who is jumping, it may be a postdoc he/she is 
> throwing.
> 
> Priority makes careers (look back at the Lavoisier/Priestly, Adams/LeVerrier 
> or
> Cope/Marsh controversies), and the history of scientific reviewing is not all 
> edifying.
> 
> Too many checks, not enough balances. Science is probably better served if the
> author can publish without passing on the pdb model to a potentially 
> unscrupulous 
> reviewer, and if there are minor errors in the published paper then a 
> competing
> group also has reason to publish its own view. The errors already have to 
> evade the
> excellent validation tools we now have thanks to so many talented programmers,
> and proper figures and tables (plus validation report) should be enough for a 
> review.
> The picture we have of haemoglobin is now much more accurate than the ones 
> which came out decades ago, but those structures were very useful in the mean 
> time. A requirement of resolution better than 2 Angstroms would probably stop 
> poor 
> models entering PDB, but I don't think it would serve science as a whole. 
> Science
> is generally a self-correcting process, rather than a demand for perfection 
> in every
> paper. Computer software follows a similar pattern - bug reports don't always 
> invalidate the
> program.
> 
> I have happily released data and coordinates via PDB before publication, even 
> back in the
> 1990s when this was unfashionable, but would not do so if I felt it risked a 
> postdoc
> failing to publish a key paper before competitors. It might be helpful if 
> journals were
> more amenable to new structures of "solved" proteins as the biology often 
> emerges 
> from several models of different conformations or ligation states. But in a 
> "publish or
> perish" world, authors need rights too. Reviewers do a necessary job, but 
> there is a
> need for balance.
> 
> The attached figure shows a French view of Le Verrier discovering Uranus, 
> while
> Adams uses his telescope for a quite different purpose.
> 


-- 

 ===
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 * Gerard Bricogne g...@globalphasing.com  *
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 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
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Re: [ccp4bb] peculiar twinning case

[Gerard Bricogne]

Dear Ed,

 You might well have a case of something called "lattice-translocation
disorder", which is indeed an intermediate type of disorder with partially
coherent interference between crystal domains related by non-lattice
translations. Take a look at a recent paper on the subject (for instance,
Acta Cryst. D65, 980-988) and at the references in it. This type of disorder
has a long and distinguished history in protein crystallography, starting
with a paper by Bragg & Howells in 1954 (Acta Cryst. 7, 409-411).

 Good luck!
 
   Gerard.

--
On Fri, Oct 15, 2010 at 06:08:09PM -0400, Ed Pozharski wrote:
> A couple of twinning-related questions.
> 
> I have a protein-DNA complex in P65.  Protein binds DNA as a dimer, DNA
> itself is not palindromic and has sticky ends located asymmetrically
> with respect to the protein (dimer).
> 
> DNA contains a single fluoro-uracil which is flipped into the active
> site.  This 3A structure can be easily refined down to Rf~35%, at which
> point difference density tracing the fluoroU and adjacent basepairs of a
> "self-superimposed" dimer is visible in the active site of the second
> monomer.
> 
> The dimer two-fold axis are aligned with the bisector of the (a,b).
> Thus my first question - do I understand correctly that this corresponds
> exactly to (k,h,-l) operator which is one of the possible twinning
> operators in P65?
> 
> When I try twin refinement in Refmac, the Rfree drops some 3%  and
> reported twinning fraction is 10%.  It's great to have the lower Rfree,
> of course, but I doubt that 10% occupancy would give me a detectable
> density (I see mainly phosphate, but the fluoro-U moiety is rather clear
> too).  And indeed, the difference density remains after accounting for
> twinning.
> 
> So I tried the "dual model", where I have two copies of the whole
> assembly, with the second one obtained by rotation around dimer axis.
> The Rfree drops another 3%, and the difference density is now accounted
> for, but the occupancy optimized for the lowest Rfree is about 50%.
> 
> Thus my second question - since twinning appears to be related to the
> same spatial transformation, why it doesn't account for it? And in more
> general sense - what is going on in this lattice?
> 
> Afaiu, the twinning and dual model contribute to the Fc in different
> ways.  For twinning part, the Fc=sqrt(|F1|^2+|F2|^2), whereas for dual
> model Fc=F1+F2 with phases included.  Now, does this mean that I somehow
> have two types of twinning in this crystal - "coherent" (at 50%) and
> incoherent (at 10%)?  Or is it that both description are correlated - in
> which case I don't understand why I get an additional drop when the two
> are combined.
> 
> It may also be important that two-fold dimer axis are not exactly (but
> close) at the bisector - the polar angles reported by superpose are
> (87.91,-116.242,179.987).
> 
> I'll appreciate any suggestions,
> 
> Ed. 
> 
> -- 
> Edwin Pozharski, PhD, Assistant Professor
> University of Maryland, Baltimore
> --
> When the Way is forgotten duty and justice appear;
> Then knowledge and wisdom are born along with hypocrisy.
> When harmonious relationships dissolve then respect and devotion arise;
> When a nation falls to chaos then loyalty and patriotism are born.
> --   / Lao Tse /

-- 

 ===
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 * Gerard Bricogne g...@globalphasing.com  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
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 ===

Re: [ccp4bb] Against Method (R)

[Gerard Bricogne]

Dear all,

 Augustine, "Confessions", Book 11 Chap. XIV, has it:
 
 "If no one ask of me, I know; if I wish to explain to him who asks, I
know not."


 With best wishes,
 
  Gerard.

--
On Tue, Oct 26, 2010 at 01:30:11PM -0500, Phoebe Rice wrote:
> Another issue with these statistics is that the PDB insists on a single value 
> of "resolution" no matter how anisotropic the data.  Especially in the 
> outermost bins, Rmerge could be ridiculously high simply because the data 
> only exist in one out of 3 directions.
>Phoebe
> 
> =
> Phoebe A. Rice
> Dept. of Biochemistry & Molecular Biology
> The University of Chicago
> phone 773 834 1723
> http://bmb.bsd.uchicago.edu/Faculty_and_Research/01_Faculty/01_Faculty_Alphabetically.php?faculty_id=123
> http://www.rsc.org/shop/books/2008/9780854042722.asp
> 
> 
>  Original message 
> >Date: Tue, 26 Oct 2010 09:46:46 -0700
> >From: CCP4 bulletin board  (on behalf of "Bernhard 
> >Rupp (Hofkristallrat a.D.)" )
> >Subject: [ccp4bb] Against Method (R)  
> >To: CCP4BB@JISCMAIL.AC.UK
> >
> >Hi Folks,
> >
> >Please allow me a few biased reflections/opinions on the numeRology of the
> >R-value (not R-factor, because it is neither a factor itself nor does it
> >factor in anything but ill-posed reviewer's critique. Historically the term
> >originated from small molecule crystallography, but it is only a
> >'Residual-value')
> >
> >a) The R-value itself - based on the linear residuals and of apparent
> >intuitive meaning - is statistically peculiar to say the least. I could not
> >find it in any common statistics text. So doing proper statistics with R
> >becomes difficult.
> >
> >b) rules of thumb (as much as they conveniently obviate the need for
> >detailed explanations, satisfy student's desire for quick answers,  and
> >allow superficial review of manuscripts) become less valuable if they have a
> >case-dependent large variance, topped with an unknown parent distribution.
> >Combined with an odd statistic, that has great potential for misguidance and
> >unnecessarily lost sleep. 
> >
> >c) Ian has (once again) explained that for example the Rf-R depends on the
> >exact knowledge of the restraints and their individual weighting, which we
> >generally do not have. Caution is advised.
> >
> >d) The answer which model is better - which is actually what you want to
> >know - becomes a question of model selection or hypothesis testing, which,
> >given the obscurity of R cannot be derived with some nice plug-in method. As
> >Ian said the models to be compared must also be based on the same and
> >identical data.  
> >
> >e) One measure available that is statistically at least defensible is the
> >log-likelihood. So what you can do is form a log-likelihood ratio (or Bayes
> >factor (there is the darn factor again, it’s a ratio)) and see where this
> >falls - and the answers are pretty soft and, probably because of that,
> >correspondingly realistic. This also makes - based on statistics alone -
> >deciding between different overall parameterizations difficult. 
> >
> >http://en.wikipedia.org/wiki/Bayes_factor
> >
> >f) so having said that, what really remains is that the model that fits the
> >primary evidence (minimally biased electron density) best and is at the same
> >time physically meaningful, is the best model, i. e., all plausibly
> >accountable electron density (and not more) is modeled. You can convince
> >yourself of this by taking the most interesting part of the model out (say a
> >ligand or a binding pocket) and look at the R-values or do a model selection
> >test - the result will be indecisive.  Poof goes the global rule of thumb.
> >
> >g) in other words: global measures in general are entirely inadequate to
> >judge local model quality (noted many times over already by Jones, Kleywegt,
> >others, in the dark ages of crystallography when poorly restrained
> >crystallographers used to passionately whack each other over the head with
> >unfree R-values).   
> >
> >Best, BR
> >-
> >Bernhard Rupp, Hofkristallrat a.D.
> >001 (925) 209-7429
> >+43 (676) 571-0536
> >b...@ruppweb.org
> >hofkristall...@gmail.com
> >http://www.ruppweb.org/
> >--
> >Und wieder ein chillout-mix aus der Hofkristall-lounge
> >--

-- 

 ===
 * *
 * Gerard Bricogne g...@globalphasing.com  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
 * *
 ===

Re: [ccp4bb] Strange spots

[Gerard Bricogne]

Dear John,

 Would it be possible to know more about what you are referring to
without having to buy (or steal) your book :-)) ?

 Thank you in advance!
 
 
 With best wishes,
 
  Gerard.

--
On Fri, Oct 29, 2010 at 06:41:51PM +0100, John R Helliwell wrote:
> Dear Dave,
> You have a collector's item there!
> The closest I have seen is illustrated in my book 'Macromolecular
> Crystallography with Synchrotron Radiation' page 321, which is a small
> molecule example.
> Best wishes,
> John
> Prof John R Helliwell DSc
> 
> 
> On Fri, Oct 29, 2010 at 5:08 PM, David Goldstone
>  wrote:
> > Dear All,
> >
> > Does anyone have any insight into what the circles around the spots might
> > be?
> >
> > cheers
> >
> > Dave
> > --
> > David Goldstone, PhD
> > National Institute for Medical Research
> > Molecular Structure
> > The Ridgeway
> > Mill Hill
> > London NW7 1AA
> >
> >
> 
> 
> 
> -- 
> Professor John R Helliwell DSc

-- 

 ===
 * *
 * Gerard Bricogne g...@globalphasing.com  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
 * *
 ===

Re: [ccp4bb] Strange spots

[Gerard Bricogne]

Dear Liz,

 You will be disappointed. I went immediately to that link, but page 321
is not available as part of the Googlebook sample, which jumps directly from
page 320 to page 325. 


 With best wishes,
 
  Gerard.

--
On Fri, Oct 29, 2010 at 09:13:27PM +0100, elizabeth.d...@diamond.ac.uk wrote:
> There is always hope!!!
>  
> Seriously though, I have never seen anything like this before! I am watching 
> this thread with interest to see what others suggest.
>  
> THanks Also thanks should go specifically to Julian Nomme who took the 
> trouble to send us all the Helliwell book  link. 
>  
> Liz
> 
> 
> 
> From: CCP4 bulletin board on behalf of Sanishvili, Ruslan
> Sent: Fri 29/10/2010 21:08
> To: CCP4BB@JISCMAIL.AC.UK
> Subject: Re: [ccp4bb] Strange spots
> 
> 
> 
> C'mon now! Everybody knows that frogs in real space become handsome princes 
> in the reciprocal one...
> 
> N.
> 
>  
> 
> Ruslan Sanishvili (Nukri), Ph.D.
> 
> GM/CA-CAT
> Biosciences Division, ANL
> 9700 S. Cass Ave.
> Argonne, IL 60439
> 
> Tel: (630)252-0665
> Fax: (630)252-0667
> rsanishv...@anl.gov 
> 
> 
> 
> From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of Jacob 
> Keller
> Sent: Friday, October 29, 2010 3:00 PM
> To: CCP4BB@JISCMAIL.AC.UK
> Subject: Re: [ccp4bb] Strange spots
> 
>  
> 
>  
> 
> Yes, but the question is what in real space gives rise to reciprocal-space 
> frog spawn? (Frogs, I guess?)
> 
>
> 
>   - Original Message - 
> 
>   From: Marcus Winter   
> 
>   To: CCP4BB@JISCMAIL.AC.UK 
> 
>   Sent: Friday, October 29, 2010 2:56 PM
> 
>   Subject: Re: [ccp4bb] Strange spots
> 
>
> 
>
> 
>
> 
>
> 
>   Dear David, 
> 
>
> 
>
> 
>   Further to the previous learned responses, surely, this 
> 
>   is just frog spawn ?
> 
>
> 
>   My apologies: it is a Friday evening, after all...
> 
>
> 
>
> 
>   Marcus Winter.
> 
>
> 
>
> 
>
> 
>   -Original Message-
>   From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of 
> David Goldstone
>   Sent: 29 October 2010 17:08
>   To: CCP4BB@JISCMAIL.AC.UK
>   Subject: [ccp4bb] Strange spots
> 
>
> 
>   Dear All,
> 
>
> 
>   Does anyone have any insight into what the circles around the spots 
> might be?
> 
>
> 
>   cheers
> 
>
> 
>   Dave
> 
>   --
> 
>   David Goldstone, PhD
> 
>   National Institute for Medical Research
> 
>   Molecular Structure
> 
>   The Ridgeway
> 
>   Mill Hill
> 
>   London NW7 1AA
> 
>
> 
>  
> 
>  
> 
> ***
> Jacob Pearson Keller
> Northwestern University
> Medical Scientist Training Program
> Dallos Laboratory
> F. Searle 1-240
> 2240 Campus Drive
> Evanston IL 60208
> lab: 847.491.2438
> cel: 773.608.9185
> email: j-kell...@northwestern.edu
> ***

Re: [ccp4bb] FW: [ccp4bb] Resolution and distance accuracies

[Gerard Bricogne]

Dear Bernhard,

 I must say that I find the "super-resolution" claims in this paper a
bit of a conjuring trick. If the final refined model has greater accuracy
than one would expect from the resolution of the data it has been refined
against, it is because that extra accuracy has been lifted from the higher
resolution data that were used to refine the structure on the basis of which
the elastic network restraints were created.

 Should we then say that we achieve super-resolution whenever we refine
a macromolecular structure using Engh & Huber restraints, because these
enable us to achieve distance accuracies comparable with those in the small
molecules structures in the Cambridge Structural Database?

 Perhaps I have missed an essential point of this paper.
 
 
 With best wishes,
 
  Gerard.

--
On Thu, Dec 23, 2010 at 12:25:26PM -0800, Bernhard Rupp (Hofkristallrat a.D.) 
wrote:
> Oops I am outdated: Axel just emailed me that he describes an improved
> coordinate estimate beyond the Rayleigh criterion in his recent paper
> 
> Schroder GF, Levitt M, & Brunger AT (2010) Super-resolution biomolecular
> crystallography with low-resolution data. Nature 464(7292), 1218-1222.
> 
> For the deformable elastic network (DEN) refinement, see his ref 14
> 
> Schroder GF, Brunger AT, & Levitt M (2007) Combining efficient
> conformational sampling with a deformable elastic network model facilitates
> structure refinement at low resolution. Structure 15(12), 1630-1641.
> 
> BR

-- 

 ===
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Re: [ccp4bb] FW: [ccp4bb] Resolution and distance accuracies

[Gerard Bricogne]

Dear Axel,

On Sun, Dec 26, 2010 at 01:15:44PM -0800, Axel Brunger wrote:
> We defined "super-resolution" in our DEN paper as
> achieving coordinate accuracy better than the resolution 
> limit  d_min of the diffraction data.  We proposed this 
> definition in analogy to its use wide-spread use in optical microscopy: 
> "super-resolution" methods such as STORM, PALM, and STED achieve
> accuracy of positions of fluorescent labels significantly better than the 
> diffraction limit (in some cases, sub-nanometer accuracy  - 
> Pertsinidis, Zhang, Chu, Nature 466, 647-651, 2010).  

 In that case, all crystallographers doing stereochemically restrained
refinement will now have become aware, to their great delight, that they
have been unknowingly achieving "super-resolution" all the time, from the
grand old days of Bob Diamond's real-space refinement program - just like
Monsieur Jourdain found out that he had been speaking in prose all his life
without realising it.

 I guess that "super-resolution" is a sexier keyword in the mind of
editors of Nature that "restrained crystallographic refinement" :-)) !


 With best wishes for the New Year,
 
   Gerard.

--
> We found DEN to be useful to move some atoms into correct 
> positions in cases where electron density maps are difficult or
> impossible to interpret at low resolution. By default, DEN is 
> active during the first torsion angle molecular dynamics stages, 
> but then turned off during the last two stages.  In addition, the
> DEN network is deformable. Thus, DEN is very different from 
> "secondary structure" restraints or point restraints to reference
> models which are "on" all the time.  Rather, DEN steers or 
> guides the torsion angle conformational search process during
> refinement. 
> 
> Cheers,
> Axel
> 
> 
> 
> On Dec 24, 2010, at 2:14 PM, Bernhard Rupp (Hofkristallrat a.D.) wrote:
> 
> >> I find the "super-resolution" claims in this paper a bit of a conjuring
> > trick. 
> > 
> > I think it is understood that information cannot come from nothing. You
> > cannot cheat in basic physics. Interestingly, I had the same discussion with
> > bioinformatics colleagues a short time ago. The problem is the same and
> > seems of a semantic nature. They are using prior information of some sort
> > (undisclosed) to successfully improve maps and they suggested to call this
> > 'resolution increase'. I had the same objection and said that in
> > crystallography resolution is a relatively hard term defined by the degree
> > to which experimental observations are available, and as crystallographers
> > we won't like that claim at all.  
> > 
> > On the other side it is uncontested that as long as the model fits
> > (crossvalidation-) data better when prior information is used, something
> > useful has been achieved - again with all the caveats of weights and bias
> > etc admitted.  
> > 
> > However, how to entice non-experts to actually use new methods is another
> > thing, and here the semantics come in. In essence, if at the end it results
> > in better structures, how much of the unfortunately but undeniably necessary
> > salesmanship is just right or acceptable? Within contemporary social
> > constraints (aka Zeitgeist) that remains pretty much an infinitely debatable
> > matter..  
> > 
> > Merry Christmas, BR
> > --
> > Dear Bernhard,
> > 
> > I must say that I find the "super-resolution" claims in this paper a
> > bit of a conjuring trick. If the final refined model has greater accuracy
> > than one would expect from the resolution of the data it has been refined
> > against, it is because that extra accuracy has been lifted from the higher
> > resolution data that were used to refine the structure on the basis of which
> > the elastic network restraints were created.
> > 
> > Should we then say that we achieve super-resolution whenever we refine
> > a macromolecular structure using Engh & Huber restraints, because these
> > enable us to achieve distance accuracies comparable with those in the small
> > molecules structures in the Cambridge Structural Database?
> > 
> > Perhaps I have missed an essential point of this paper.
> > 
> > 
> > With best wishes,
> > 
> >  Gerard.
> 
> Axel T. Brunger
> Investigator,  Howard Hughes Medical Institute
> Professor of Molecular and Cellular Physiology
> Stanford University
> 
> Web:http:/

Re: [ccp4bb] Fwd: [ccp4bb] FW: [ccp4bb] Resolution and distance accuracies

[Gerard Bricogne]

Dear Colin,

 Wladek Minor has just drawn my attention to the following recent paper:
 
  Acta Cryst. (2010). D66, 1041.1042

(that I must admit to having failed to notice) also expressing reservations
about some uses of "creative language". 


 With best wishes,
 
  Gerard.

--
On Thu, Jan 06, 2011 at 11:13:41AM -, Colin Nave wrote:
> I too think the phrase super-resolution is rather misleading, in particular 
> the analogy with light microscopy methods. Super-resolution in these latter 
> cases is achieved via different physical phenomena (think excitations not 
> waves). 
> 
>  
> 
> Would one claim super-resolution when refining the relative positions of the 
> carbon atoms in benzene given the constraints of 6 fold symmetry and a carbon 
> carbon distance of 1.39 angstroms?
> 
>  
> 
> What would Moliere think? 
> 
>  
> 
> However, to quote from the DEN paper
> 
> "Our approach is a major advance over conventional modeling of low resolution 
> X-ray diffraction data by fitting rigid bodies since it accounts for 
> deformations of the models while at the same time using a minimal set of 
> variables (the single-bond torsion angles)"
> 
>  
> 
> Overall this seems a reasonable claim.
> 
> Colin
> 
>  
> 
> From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of Charles 
> W. Carter, Jr
> Sent: 06 January 2011 09:52
> To: CCP4BB@JISCMAIL.AC.UK
> Subject: [ccp4bb] Fwd: [ccp4bb] FW: [ccp4bb] Resolution and distance 
> accuracies
> 
>  
> 
>  
> 
>  
> 
> Begin forwarded message:
> 
> 
> 
> 
> 
> From: "Charles W. Carter, Jr" 
> 
> Date: January 6, 2011 10:51:20 AM GMT+01:00
> 
> To: Gerard Bricogne 
> 
> Subject: Re: [ccp4bb] FW: [ccp4bb] Resolution and distance accuracies
> 
>  
> 
> I echo Gérard's thought. 
> 
>  
> 
> Pascal Retailleau did a relevant experiment published in Acta D:
> 
>  
> 
> Retailleau, et al., (2001) High-resolution experimental phases for 
> tryptophanyl-tRNA synthetase
> 
> (TrpRS) complexed with tryptophanyl-5'AMP, Acta Cryst, D57, 1595-1608
> 
>  
> 
> He determined three independent sets of experimental phases for two different 
> 1.7 Å selenomethionine structures (SAD) plus a 1.6 Å native (MIRAS) and 
> refined the structures independently. The rmsd between the two SeMet 
> structures was 0.25 Å, whereas that between the two SAD structures and the 
> native structure was 0.39 Å, sufficient to demonstrate significant 
> differences between the SeMet and native proteins. This experimental variance 
> is a quite considerable indication of the magnitude of coordinate errors.
> 
>  
> 
> Thus, as Gérard, who also was an author on that work together with Bob Sweet, 
> points out, we're delighted to discover we have been achieving 
> super-resolution to use Axel's neologism!
> 
>  
> 
> Charlie
> 
>  
> 
>  
> 
>  
> 
> On Jan 6, 2011, at 10:13 AM, Gerard Bricogne wrote:
> 
> 
> 
> 
> 
> Dear Axel,
> 
> On Sun, Dec 26, 2010 at 01:15:44PM -0800, Axel Brunger wrote:
> 
> 
> 
> We defined "super-resolution" in our DEN paper as
> 
>   achieving coordinate accuracy better than the resolution 
> 
>   limit  d_min of the diffraction data.  We proposed this 
> 
>   definition in analogy to its use wide-spread use in optical microscopy: 
> 
>   "super-resolution" methods such as STORM, PALM, and STED achieve
> 
>   accuracy of positions of fluorescent labels significantly better than 
> the 
> 
>   diffraction limit (in some cases, sub-nanometer accuracy  - 
> 
>   Pertsinidis, Zhang, Chu, Nature 466, 647-651, 2010).  
> 
> 
> In that case, all crystallographers doing stereochemically restrained
> refinement will now have become aware, to their great delight, that they
> have been unknowingly achieving "super-resolution" all the time, from the
> grand old days of Bob Diamond's real-space refinement program - just like
> Monsieur Jourdain found out that he had been speaking in prose all his life
> without realising it.
> 
> I guess that "super-resolution" is a sexier keyword in the mind of
> editors of Nature that "restrained crystallographic refinement" :-)) !
> 
> 
> With best wishes for the New Year,
> 
>   Gerard.
> 
> --
> 
> 
> 
> We found DEN to be useful to move some atoms into correct 
> 
>   positions in cases where electron density maps are difficult or
> 
>   impossible to 

Re: [ccp4bb] what to do with disordered side chains

[Gerard Bricogne]

Dear Quyen,

On Thu, Mar 31, 2011 at 11:27:58AM -0400, Quyen Hoang wrote:
> Thank you for your post, Herman.
> Since there is no holy bible to provide guidance, perhaps we should hold 
> off the idea of electing a "powerful dictator" to enforce this?
> - at least until we all can come to a consensus on how the "dictator" 
> should dictate...
>

 ... but that might well be even harder than to decide what to do with
disordered side chains ... .


 With best wishes,
 
  Gerard.

--

 ===
 *     *
 * Gerard Bricogne g...@globalphasing.com  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
 * *
 ===
>
>
> On Mar 31, 2011, at 10:22 AM, herman.schreu...@sanofi-aventis.com wrote:
>
>> Dear Quyen,
>> I am afraid you won't get any better answers than you got so far. There is 
>> no holy bible telling you what to do with disordered side chains. I fully 
>> agree with James that you should try to get the best possible model, which 
>> best explains your data and that will be your decision. Here are my 2 
>> cents:
>>
>> -If you see alternative positions, you have to build them.
>> -If you do not see alternative positions, I would not replace one fantasy 
>> (some call it most likely) orientation with 2 or 3 fantasy orientations.
>> -I personally belong to the "let the B-factors take care of it" camp, but 
>> that is my personal opinion. Leaving side chains out could lead to 
>> misinterpretations by slightly less savy users of our data, especially 
>> when charge distributions are being studied. Besides, we know (almost) for 
>> sure that the side chain is there, it is only disordered and as we just 
>> learned, even slightly less savy users know what flaming red side chains 
>> mean. Even if they may not be mathematically entirely correct, huge 
>> B-factors clearly indicate that there is disorder involved.
>> -I would not let occupancies take up the slack since even very savy users 
>> have never heard of them and again, the side chain is fully occupied, only 
>> disordered. Of course if you build alternate positions, you have to divede 
>> the occupancies amongst them.
>>
>> Best,
>> Herman
>>
>> From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of 
>> Quyen Hoang
>> Sent: Thursday, March 31, 2011 3:55 PM
>> To: CCP4BB@JISCMAIL.AC.UK
>> Subject: Re: [ccp4bb] what to do with disordered side chains
>>
>> We are getting off topic a little bit.
>>
>> Original topic: is it better to not build disordered sidechains or build 
>> them and let B-factors take care of it?
>> Ed's poll got almost a 50:50 split.
>> Question still unanswered.
>>
>> Second topic introduced by Pavel: "Your B-factors are valid within a 
>> harmonic (small) approximation of atomic vibrations. Larger scale motions 
>> you are talking about go beyond the harmonic approximation, and using the 
>> B-factor to model them is abusing the corresponding mathematical model."
>> And that these large scale motions (disorders) are better represented by 
>> "alternative conformations and associated with them occupancies".
>>
>> My question is, how many people here do this?
>> If you're currently doing what Pavel suggested here, how do you decide 
>> where to keep the upper limit of B-factors and what the occupancies are 
>> for each atom (data with resolution of 2.0A or worse)? I mean, do you cap 
>> the B-factor at a reasonable number to represent natural atomic vibrations 
>> (which is very small as Pavel pointed out) and then let the occupancies 
>> pick up the slack? More importantly, what is your reason for doing this?
>>
>> Cheers and thanks for your contribution,
>> Quyen
>>
>>
>> On Mar 30, 2011, at 5:20 PM, Pavel Afonine wrote:
>>
>>> Mark,
>>> alternative conformations and associated with them occupancies are to 
>>> describe the larger scale disorder (the one that goes beyond the 
>>> B-factor's capability to cope with).
>>> Multi-model PDB files is another option.
>>> Best,
>>> Pavel.
>>>
>>

Re: [ccp4bb] problem of conventions

[Gerard Bricogne]

Dear Boaz,

 I think you are the one who is finally asking the essential question. 
 
 The classification we all know about, which goes back to the 19th
century, is not into 230 space groups, but 230 space-group *types*, i.e.
classes where every form of equivalencing (esp. by choice of setting) has
been applied to the enumeration of the classes and the choice of a unique
representative for each of them. This process of maximum reduction leaves
very little room for the introducing "conventions" like a certain ordering
of the lengths of cell parameters. This seems to me to be a major mess-up in
the field - a sort of "second-hand mathematics by (IUCr) committee" which
has remained so ill-understood as to generate all these confusions. The work
on the derivation of the classes of 4-dimensional space groups explained the
steps of this classification beautifully (arithmetic classes -> extension by
non-primitive translations -> equivalencing under the action of the
normaliser), the last step being the choice of a privileged setting *in
termns of the group itself* in choosing the representative of each class.
The extra "convention" a Excuse my naive (perhaps ignorant) question: when was the
>  a textbooks I came across mentions it as far as I could see (not that this is 
> reason for or against this rule of course).
> 
>     Thanks,
> 
>    Boaz
> 
> 
> Boaz Shaanan, Ph.D.
> Dept. of Life Sciences
> Ben-Gurion University of the Negev
> Beer-Sheva 84105
> Israel
> Phone: 972-8-647-2220 ; Fax: 646-1710
> Skype: boaz.shaanan‎

-- 

 ===
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 * Gerard Bricogne g...@globalphasing.com  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
 * *
 ===

Re: [ccp4bb] XXII IUCr Congress and General Assembly - Madrid (Spain)

[Gerard Bricogne]

Dear Harry,

 Thank you for the reminder. Upon connecting to the URL given in
Martin's e-mail, however, one immediately gets a pop-up saying:

   "New deadline fo abstract submission: April 28"

(no doubt to enable everyone to work until the last minute prior to the
royal wedding ...). Can you confirm?


 With best wishes,
 
  Gerard.

--
On Fri, Apr 15, 2011 at 11:39:14AM +0100, Harry Powell wrote:
> Hi folks
> 
> today is the last day to get your abstract in!
> 
> On 7 Apr 2011, at 14:24, Martin M. Ripoll wrote:
> 
> > Dear colleagues,
> >  
> > This is just to remind you that the “XXII Congress and General Assembly” of 
> > the IUCr (International Union of Crystallography) will be held in Madrid 
> > (Spain) from 22-30 August 2011 and that your Spanish colleagues kindly 
> > invite you to participate not only in the most important crystallographic 
> > event until 2014, but also to enjoy a fruitful meeting in a sunny and full 
> > of life city!
> >  
> > All information is to be found in:
> > http://www.iucr2011madrid.es/
> > although two important dates to remember are:
> > April 15, 2011: Deadline for abstracts submission
> > May 15,  2011: Deadline for "Early bird" registration
> >  
> > All the best and see you in Madrid!
> >  
> > On behalf of the Organizing Committee,
> >  
> > Martin (Vice-Chairman)
> > 
> > Dr. Martin Martinez-Ripoll
> > Research Professor
> > xmar...@iqfr.csic.es
> > Department of Crystallography & Structural Biology
> > www.xtal.iqfr.csic.es
> > Telf.: +34 917459550
> > Consejo Superior de Investigaciones Científicas
> > Spanish National Research Council
> > www.csic.es
> > 
> >  
> 
> Harry
> --
> Dr Harry Powell 
> Chairman ECA SIG9 (Crystallographic Computing) 
> Acting Chairman IUCr Commission on Crystallographic Computing 
> 
> http://www.iucr.org/resources/commissions/crystallographic-computing/schools/mieres2011
> 

-- 

 ===
 * *
 * Gerard Bricogne g...@globalphasing.com  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
 * *
 ===

Re: [ccp4bb] Lattice sampling and resolution - a seeming paradox?

[Gerard Bricogne]

to +h would be used, which gives twice the number of
>>> Fourier coefficients, but the underlying sampling of the unit cell along 
>>> a
>>> with maximum index |h| is still only a/h!
>>>
>>> This leads to my seeming paradox: according to Braggs law and the von 
>>> Laue
>>> conditions, I get the information at resolution d already with a 1x 
>>> sampling
>>> a/h, but according to the Nyquist-Shannon sampling theory, I would need a 
>>> 2x
>>> sampling a/(2h).
>>>
>>> So what is the argument again, that the sampling of the continuous 
>>> molecular
>>> transform imposed by the crystal lattice is sufficient to get the desired
>>> information at a given resolution?
>>>
>>> I would be very grateful for your help!
>>>
>>> Best regards,
>>>
>>> Dirk.
>>>
>>> --
>>>
>>> ***
>>> Dirk Kostrewa
>>> Gene Center Munich, A5.07
>>> Department of Biochemistry
>>> Ludwig-Maximilians-Universität München
>>> Feodor-Lynen-Str. 25
>>> D-81377 Munich
>>> Germany
>>> Phone:  +49-89-2180-76845
>>> Fax:+49-89-2180-76999
>>> E-mail: kostr...@genzentrum.lmu.de
>>> WWW:www.genzentrum.lmu.de
>>> ***
>>>
>
> -- 
>
> ***
> Dirk Kostrewa
> Gene Center Munich, A5.07
> Department of Biochemistry
> Ludwig-Maximilians-Universität München
> Feodor-Lynen-Str. 25
> D-81377 Munich
> Germany
> Phone:+49-89-2180-76845
> Fax:  +49-89-2180-76999
> E-mail:   kostr...@genzentrum.lmu.de
> WWW:  www.genzentrum.lmu.de
> ***

-- 

 ===
 * *
 * Gerard Bricogne g...@globalphasing.com  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
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Re: [ccp4bb] Workshop on "Soft X-ray Crystallography" at the APS, May 4, 2011

[Gerard Bricogne]

Dear BC and colleagues,

 It is rather unclear from the title of the workshop whether it is the
Crystallography that will be soft, or the X-rays.


 With best wishes,
 
  Gerard.

--
On Fri, Apr 22, 2011 at 11:56:22AM -0400, Bi-Cheng Wang wrote:
> We would like to call your attention to a workshop associated with the 
> upcoming 2011 APS Users Meeting, which will be held on May 4, 2011 at the 
> APS, Argonne National Laboratory, USA. 
>  
> The title of the workshop is  “Soft X-ray Crystallography”.  You may find the 
> workshop program at 
> 
> http://2011usersmeeting.conference.anl.gov/APSWK1Agenda.htm
>  
> The web links for meeting registration and the application for a permit to 
> enter the Argonne National Laboratory are:
>  
> https://2011usersmeeting.conference.anl.gov/register
> 
> http://www.aps.anl.gov/Users/Site_Access
>  
> We hope you will be able to attend the APS Users Meeting and our workshop.
>  
> All the best,
>  
> B.C. Wang, John Rose, Gerd Rosenbaum and John Chrzas.
-- 

 ===
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 * Gerard Bricogne g...@globalphasing.com  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
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 ===

Re: [ccp4bb] Dehydration treatments

[Gerard Bricogne]

Dear Israel,

 There is a lot to look up in this field. I believe it started with
 
   Schick, B. & Jurnak, F. (1994). Acta Cryst. D50, 563-568.

at   http://scripts.iucr.org/cgi-bin/paper?gr0289

There is a nice review online at 

  http://www-bio3d-igbmc.u-strasbg.fr/~mgsb/biophys/rx/biblio/heras_2005.pdf

and then of course there has been the development of the Free-Mounting
System by Proteros:

  http://www.proteros.com/articles.php?sid=18&lang=de

based on a different method of hydration control.


 Good luck!
 
   Gerard.

--
On Sun, May 01, 2011 at 06:32:21PM +0100, Israel Sanchez wrote:
> Hi folks,
> 
> 
> I am currently impressed by the efficiency of dehydration treatments over
> the diffraction capacity of our crystals in one particular condition.
> Without any treatment the crystals seldom diffract to 20-30A but in our last
> synchrotron trip the very same crystals, after been incubated with
> increasing concentration of low molecular weight PEGs diffracted to 6A.
> 
> I was wondering if anyone has studied these effects in a systematic way.
> Does anyone on the ccp4bb knows  references or has any
> experience/pseudo-religious believes that do not care to share with the
> community about this particular topic?
> 
> 
> Thank you very much in advance
> 
> 
> -- 
>  Israel Sanchez Fernandez PhD
> Ramakrishnan-lab
> MRC Laboratory of Molecular Biology,
> Hills Road, Cambridge, CB2 0QH, UK

-- 

 ===
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 * Gerard Bricogne g...@globalphasing.com  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
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Re: [ccp4bb] Buster

[Gerard Bricogne]

Dear Xavier,

 I am very sorry that I didn't respond instantly to your query about
this strange observation at the beginning of the month. After that, it was
sitting rather invisibly in my mailbox, given that its subject line said
"Re: [ccp4bb] Dehydration treatments" :-) .

 We are just about to release a new version of BUSTER in conjunction
with the final session of the ACA meeting. However, let us deal with your
question off-list, as it isn't related to ccp4.

 I will be in touch.
 
 
 With best wishes,
 
  Gerard.

--
On Fri, May 27, 2011 at 04:57:04PM +0200, "F.Xavier Gomis-Rüth" wrote:
> Dear CCP4ers,
> I start apologizing for this off-topic question but I could not get an 
> answer knocking at other doors...
> We have installed version 1.6.0. from July 18,2009 of BUSTER, which 
> apparently has a slight problem:
> after each refinement step, I need to "re-center" the model within the new 
> electron density map.
> Is there any means to circumvent this ? Is there any newer version 
> available somewhere ?
> I could not find any indication in the web page of Global Phasing  but 
> think it is rather strange that there has been
> no release since almost two years.
> Thanks a lot in advance,
> Xavier
> -- 

-- 

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Re: [ccp4bb] International Symbol for sin(theta)/lambda

[Gerard Bricogne]

The most extreme degree of confusion (or at least of requirement for fast
mental arithmetic) I have come across in relation to this topic is the habit
of small-molecule crystallographers working on accurate density studies to
characterise the resolution limit of their datasets by quoting the maximum
value of sin(theta)/lambda in Angstrom^-1. Upon being told of a dataset
"with a resolution of 1.25 in sin(theta)/lambda" you have to quickly deduce
that the maximum d* value is 2.50 and therefore, in protein crystallographer
lingo, the resolution limit dmin is 0.40 Angstrom. Then, you start feeling
very envious.


With best wishes,

 Gerard.

--
On Thu, Jun 30, 2011 at 02:07:28PM -0400, Richard Edward Gillilan wrote:
> This has been a point of confusion
> 
> Here are the conventions used in a few of the classic SAXS text vs. recent 
> reviews:
> 
> --
> I believe Guinier actually used the variable "u" in his thesis, but must have 
> changed at some point (I don't have it handy to check at the moment).
> 
> Guinier & Fournet (1955)   h = 4pi Sin(theta)/lambda   where 2*theta = 
> scattering angle
> 
> Glatter & Kratky (1982) (including chapters by Porod and other authors)  
> h = 4pi Sin(theta)/lambda
> 
> --- so "h" makes sense if one is familiar with crystallography derivations. 
> 
> Feigin & Svergun (1987) s = 4pi Sin(theta)/lambda   
> 
> The notation "s" seems to come from the notation for "scattering" vectors.
> 
> Svergun publications consistently use s this way, though the software can 
> define s with or without the 2pi and in either inverse nanometers or inverse 
> Angstroms. In my experience very few use 2Sin(theta)/lambda, though it is 
> more familiar to crystallographers as the inverse of the d-spacing.
> 
> But "q" is widely used in BioSAXS:
> 
> Putnam, Hammel, Hura & Tainer (2007)   q = 4 pi Sin(theta)/lambda
> Jacques and Trewhella (2010)q = 4 pi Sin(theta)/lambda
> 
> Why q? I haven't traced it back yet. From generalized coordinate of classical 
> mechanics maybe?
> 
> 
> 
> On Jun 30, 2011, at 3:37 AM, James Stroud wrote:
> 
> > Hello All,
> > 
> > Is there precedent or a conventional shorthand (e.g. greek letter) for 
> > sin(theta)/lambda?
> > 
> > Thanks in advance for any help or suggestions.
> > 
> > James

-- 

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Re: [ccp4bb] anomalous difference fourier maps

[Gerard Bricogne]

Dear all,

 This is a remark I have wanted to make for a long time but managed so
far to repress. However, this case is absolutely clear: Ivan was not asking
for general advice on how to carry out a general task, but how to perform a
specific task with the CCP4 software.

 In response we get (surprise, surprise, ...) another instance of the
relentless touting for Phenix on the CCP4BB, which has long been an 
expected (or tolerated?) feature of this BB. Contributions from Phenix
developers are of course much appreciated when questions are about general
crystallographic matters where their expertise and experience is valuable;
but when people ask specifically how to do something with CCP4 programs,
could they please not be grabbed by the sleeve and enticed to buy their
sweets from the shop next door? 

 In this case, for instance, Ivan thanks "guys" (plural) for the answers
he got ("All of your suggestions were great"). Perhaps one of those was a
CCP4-based answer, but if so it has not even been communicated to the rest
of the CCP4BB subscribers - so not only is this touting in bad taste after a
while: it even interferes with the sharing of expertise in using the CCP4
software, which after all must be one of the main missions of this BB.

 I have long wondered whether anyone on the CCP4 side been assigned the
task of answering every question to the Phenix BB by describing how to do it
with CCP4 programs ... .


 With best wishes,
 
  Gerard.

--
On Thu, Feb 18, 2010 at 03:53:02PM -0800, Pavel Afonine wrote:
> Hi Ivan,
>
> two ways (at least) to do it in PHENIX:
>
> - phenix.refine always computes anomalous difference Fourier map (provided 
> that your input data file contains Fobs(+) and Fobs(-)). The command below 
> will do it:
>
> phenix.refine model.pdb data.mtz strategy=none 
> main.number_of_macro_cycles=0 output.prefix=maps_only
>
> - you can use phenix.maps that is a general tool to compute a broad variety 
> of maps. Type "phenix.maps" from the command line for usage instructions. 
> You need to have the latest development (or one of) PHENIX nightly build 
> for this.
>
> All this is available from the GUI too.
>
> Pavel.
>
>
> On 2/18/10 3:34 PM, xaravich ivan wrote:
>>
>> Hello,
>>
>>
>> I wanted to make an anomalous difference fourier map of a structure with 
>> zinc bound to it. However I have not been successful in making the map and 
>> I would really appreciate your help if anyone could suggest me where I am 
>> going wrong.
>>
>> I solved this zinc bound structure, by molecular replacement from a 
>> calcium bound structure (1.4 angstrom) that I solved. I want to show that 
>> the zinc binds to the identical site by the anomalous difference fourier 
>> map.
>>
>> I am using CCP4i and the steps that I have been taking are, (names of the 
>> files are arbitrary)
>>
>> 1) generating structure factors and phases from the solved coordinates by 
>> SFALL
>>
>>   Input files
>>   zinc bound pdb
>>   original zinc .mtz data from synchrotron
>>
>>  output file
>> sfall.mtz
>>
>> 2)merging the sfall.mtz containing the PHICalc and FCalc columns with 
>> the original synchrotron .mtz file containing DANO and SIGDANO by running 
>> CAD.
>>
>>  input files
>> sfall.mtz and zinc synchrtron .mtz
>>
>> output file
>> CAD.mtz
>>
>> 3) Running FFT to make anomalous map, selecting labels from CAD.mtz as 
>> input files.
>>
>> There is an output map file but nothing in it. all the values are 0 and 
>> the map is not recognized by coot. There is no error message in the log 
>> file.
>>
>>  
>> I must be missing something or doing something wrong/stupid.
>>
>>
>> Thanks,
>>
>> Ivan
>>

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Re: [ccp4bb] anomalous difference fourier maps

[Gerard Bricogne]

Dear Ivan,

 It is great to have confirmation that you got answers to your initial
question that enabled you to solve your problem. The idea of the BB is that,
in exchange for the gift of other people's contribution to solving your
problem, you are expected to share the solution with the other subscribers.
If you look through the archives, you will see numerous cases when people
who received contributions, either as replies to the BB or in messages sent
to them off-board, then took the trouble to collect them into a message to
the BB as a whole, so that everyone learned something. It would be really
good if you could do the same with the answers you got.

 I think I will bow out of this "thread" by retracting any churlish
content in my previous posting. I felt it was not quite satisfactory that a
question asked in terms of CCP4 programs should only leave a Phenix-based
solution as a written trace - but avoiding this takes some work from the
beneficiaries of the answers and not just a modicum of tact from the
repliers in answering the questions that are actually being asked.

 Of course, any broadening of subject matter beyond the initial specific
question asked is a wonderful thing to see happen in any scientific forum;
but this was not at all the case in this particular instance.


 With best wishes,
 
  Gerard.


--
On Fri, Feb 19, 2010 at 08:13:26AM -0800, xaravich ivan wrote:
> ok I think I should say something here.For some reason I was unable to find
> REPLY-ALL button and my reply did not go to everyone first so I had to write
> another message.I got the answer to my original query and I used CCP4 (CAD)
> and coot as suggested by Jan.
> Having said that I did not know that you could do it in so many ways. and
> that is perhaps the most valuable thing!!!
> Thanks all of you for your replies and I think the best thing of this forum
> is to be able to get answers when you do not have anyone in the lab to guide
> you. People like us need you guys the most. Irrespective of whether it is
> ccp4bb or phenix or any other program, the goal is to share the knowledge
> and help the less experienced (less fortunate) with your vast expertise, so
> that people can enjoy doing exciting crystallography related research.
> 
> Thanks to everyone,
> 
> Ivan
> 
> On Fri, Feb 19, 2010 at 7:37 AM, Edward A. Berry  wrote:
> 
> > The guidelines for the CCP4BB are extremely broad and certainly include
> > discussion of other software packages. Since the original poster's question
> > had to do with a specific problem with CCP4, it would have been appropriate
> > for Pavel to prefix his reply with something like "I hope you receive an
> > answer to your question shortly, but in the meantime here is an
> > alternative".
> > But this is a nicety I would be glad to forgo for the sake of getting the
> > extra information. The problem is not that the phenix team was so quick
> > to promote their software, but rather that now 14 hours after the original
> > post, no one has answered the CCP4 question. It is too easy to say "yes,
> > I think I could help this guy, but half the readers of this BB could
> > probably give a better answer".  Maybe someone at CCP4 should be assigned
> > to answer all reasonable queries that go unanswered for more than 8 hours.
> > The phenomenal rise in popularity of the phenix package is probably due as
> > much to the incredible responsiveness of the phenix team, not only in
> > support
> > but in adding requested features, as it is to the power and ease of use of
> > the programs.
> >
> >
> >
> >
> > Vellieux Frederic wrote:
> >
> >> Hi Dirk,
> >>
> >> When it happens that I reply to a ccp4bb message and that the answer, or
> >> solution I may have (which I think is "better" or "more appropriate")
> >> involves using non-ccp4 programs, I do it off-list. By replying
> >> privately to the person who asked the question.
> >>
> >> Fred.
> >>
> >> Dirk Kostrewa wrote:
> >>
> >>> Dear Gerard,
> >>>
> >>> I can only agree with you - I've also noticed a growing and sometimes
> >>> irritating cross-advertisement of non-CCP4 programs on the CCP4BB over
> >>> the last months (mainly Phenix). Unless, the specific task that was
> >>> asked for, can only be (reasonably) solved with non-CCP4 programs,
> >>> such replies leave a somewhat bad aftertaste.
> >>> Personally, I think, it would be perfectly acceptable if both
> >>> solutions with CCP4 programs and other programs would be given, so
> >>> that the user may choose, or try them all.
> >>>
> >>> Best wishes,
> >>>
> >>> Dirk.
> >>>

Re: [ccp4bb] units of f0, f', f''

[Gerard Bricogne]

Dear all,

 I think Marc has hit the nail on the head: somehow the dictatorship of
journal editors and of rules (fetishes?) for filling tables and specifying
units has made everyone so insecure as to doubt even the fundmental notions
of set theory and of the cardinality of sets. 

 There is the axiomatic definition of integers by Peano's axioms, and
then there is Cantor's definition of the cardinality of sets where the
cardinal number of a set A is the class of all the sets B that can be put in
one-to-one correspondence with A. One can then show that integers are a
particular case of cardinal numbers: the cardinal number associated to the
integer 0 is the class of all sets having no members (e.g. the void set);
the cardinal number associated to the integer 1 is the class of all sets in
one-to-one correspondence with the set {0}; and given a cardinal number
associated to the integer m, one can get that associated to the successor of
m by considering the class of sets obtained by taking the disjoint union of
each of the sets in the class defining that cardinal and of {0}. Cardinals
are more powerful than integers because they can be infinite, and even
transfinite.

 With this in mind, you can say that you have the same number of apples
as of oranges if you can associate one apple to each orange and vice-versa.
The set of apples and that of oranges have the same cardinal, and that
cardinal is uniquely associated to an integer, the "number" of both apples
and oranges. You cannot add apples and oranges, but you can add the integers
to which the cardinals of the two sets are associated, to get the cardinal
of a set to which both apples and oranges belong, e.g. of that of (pieces
of) fruit.

 Marc was correct in pointing out the "anonymity" of numbers used to
"count things", i.e. of cardinal numbers: this anonymisation is produced by
the process of forgetting what things are, as long as you can put them in
one-to-one correspondence with each other. So indeed, the "unit" of a count
is the integer 1, i.e. the cardinal of the set {0}. Of course, if we say
that f"=7.8 this is not an integer; but the next chapter of any book on set
theory would explain how one progresses from integers to rational and real
numbers.


 I apologise for this non-CCP4 answer to the initial question!
 
 
 With best wishes,
 
  Gerard.


--
On Sat, Feb 27, 2010 at 11:49:25AM +0100, marc.schi...@epfl.ch wrote:
> Quoting Dale Tronrud :
>
>>
>> P.S. to respond out-of-band to Dr. Schiltz: On the US flag I see 7 "red 
>> stripes",
>> 6 "white stripes", and 50 "stars".  If I state "I see 7" I have conveyed 
>> no
>> useful information.
>
>
> Yes, but cast in a mathematical equations one would write :
>
> Number of red stripes = 7
> Number of white stripes = 6
> Number of stars = 50
>
> i.e. without units
>
> one would not write :
>
> Number = 7 red stripes
> Number = 6 white stripes
> Number = 50 stars
>
>
> Marc

-- 

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Re: [ccp4bb] units of f0, f', f''

[Gerard Bricogne]

so let's say:
>>
>> Notation
>> 
>> f: "atomic scattering factor", defined as the ratio of scattered amplitude 
>> for an atom to that for a free electron (dimensionless).
>> g: "atomic scattering free point equivalent charge", defined as the free 
>> point charge which scatters with the same amplitude as the atom 
>> (dimensions of electric charge).
>>
>> Now we can validly write 'g = 10e' since we have dimensions of charge on 
>> both sides.
>>
>> This again highlights the importance of 1) rigorously defining all 
>> quantities in use, and 2) that the definition and the dimensions are 
>> linked: you cannot arbitrarily change the dimensions of some quantity 
>> without also changing its definition, or vice versa; and in particular you 
>> can't mix the definition of 'f' with the units of 'g', which is what seems 
>> to be happening here!
>>
>> This logical inconsistency can only be resolved by recognising that 'f' is 
>> a pure number so removing the 'e' unit.  The same argument obviously 
>> applies to anything derived from 'f' such as the structure factor and the 
>> electron density.
>>
>> Cheers
>>
>> -- Ian
>>
>>
>> Disclaimer
>> This communication is confidential and may contain privileged information 
>> intended solely for the named addressee(s). It may not be used or 
>> disclosed except for the purpose for which it has been sent. If you are 
>> not the intended recipient you must not review, use, disclose, copy, 
>> distribute or take any action in reliance upon it. If you have received 
>> this communication in error, please notify Astex Therapeutics Ltd by 
>> emailing i.tic...@astex-therapeutics.com and destroy all copies of the 
>> message and any attached documents. Astex Therapeutics Ltd monitors, 
>> controls and protects all its messaging traffic in compliance with its 
>> corporate email policy. The Company accepts no liability or responsibility 
>> for any onward transmission or use of emails and attachments having left 
>> the Astex Therapeutics domain.  Unless expressly stated, opinions in this 
>> message are those of the individual sender and not of Astex Therapeutics 
>> Ltd. The recipient should check this email and any attachments for the 
>> presence of computer viruses. Astex Therapeutics Ltd accepts no liability 
>> for damage caused by any virus transmitted by this email. E-mail is 
>> susceptible to data corruption, interception, unauthorized amendment, and 
>> tampering, Astex Therapeutics Ltd only send and receive e-mails on the 
>> basis that the Company is not liable for any such alteration or any 
>> consequences thereof.
>> Astex Therapeutics Ltd., Registered in England at 436 Cambridge Science 
>> Park, Cambridge CB4 0QA under number 3751674
>>
>>   

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Re: [ccp4bb] units of f0, f', f''

[Gerard Bricogne]

Dear Ian,

 Perhaps I should have made a more explicit connection to your message
in what I wrote yesterday. I do not think there is any paradox, or apples
vs. oranges problem, in this situation.

 The structure factor is a count of "electrons as X-ray scatterers", so
that the Fourier synthesis computed from them is a number density for these
unit scatterers. The density can get clothed with a charge a-posteriori,
because we know what the charge of an electron is, but it is not that charge
as such that is sensed by the diffraction experiment: it is the complicated
combination of charge and mass and various physical constants that ends up
determining an electron's ability to scatter X-rays. 

 I think that if one bears this in mind at all times, paradoxes never
appear.


 With best wishes,
 
  Gerard.

--
On Sun, Feb 28, 2010 at 02:40:15PM -, Ian Tickle wrote:
> 
> > Yes, I think this is exactly the point. 'Electrons' gives the whole 
> > thing a consistent meaning. 
> 
> The big problem with statements like 'f = 10e' or 'rho = 1.5e/Å^3' is of 
> course that they are dimensionally invalid, and I'm surprised that people are 
> not doing such simple checks!  For example I think we've all agreed that 'f' 
> is defined as the ratio of two amplitudes and is therefore dimensionless, 
> whereas 'e' is universally defined as the electronic charge, which in SI 
> units has the value 1.602176487×10^−19 coulombs, but obviously has the 
> dimensions of electric charge (time*electric current in terms of the base SI 
> dimensions).  So we have a real apples & oranges situation!
> 
> You could of course get around this by redefining 'f' as I suggested 
> previously, as the free point equivalent charge, but to avoid confusion we 
> should call it something else, so let's say:
> 
> Notation
> 
> f: "atomic scattering factor", defined as the ratio of scattered amplitude 
> for an atom to that for a free electron (dimensionless).
> g: "atomic scattering free point equivalent charge", defined as the free 
> point charge which scatters with the same amplitude as the atom (dimensions 
> of electric charge).
> 
> Now we can validly write 'g = 10e' since we have dimensions of charge on both 
> sides.
> 
> This again highlights the importance of 1) rigorously defining all quantities 
> in use, and 2) that the definition and the dimensions are linked: you cannot 
> arbitrarily change the dimensions of some quantity without also changing its 
> definition, or vice versa; and in particular you can't mix the definition of 
> 'f' with the units of 'g', which is what seems to be happening here!
> 
> This logical inconsistency can only be resolved by recognising that 'f' is a 
> pure number so removing the 'e' unit.  The same argument obviously applies to 
> anything derived from 'f' such as the structure factor and the electron 
> density.
> 
> Cheers
> 
> -- Ian
> 
> 
> Disclaimer
> This communication is confidential and may contain privileged information 
> intended solely for the named addressee(s). It may not be used or disclosed 
> except for the purpose for which it has been sent. If you are not the 
> intended recipient you must not review, use, disclose, copy, distribute or 
> take any action in reliance upon it. If you have received this communication 
> in error, please notify Astex Therapeutics Ltd by emailing 
> i.tic...@astex-therapeutics.com and destroy all copies of the message and any 
> attached documents. 
> Astex Therapeutics Ltd monitors, controls and protects all its messaging 
> traffic in compliance with its corporate email policy. The Company accepts no 
> liability or responsibility for any onward transmission or use of emails and 
> attachments having left the Astex Therapeutics domain.  Unless expressly 
> stated, opinions in this message are those of the individual sender and not 
> of Astex Therapeutics Ltd. The recipient should check this email and any 
> attachments for the presence of computer viruses. Astex Therapeutics Ltd 
> accepts no liability for damage caused by any virus transmitted by this 
> email. E-mail is susceptible to data corruption, interception, unauthorized 
> amendment, and tampering, Astex Therapeutics Ltd only send and receive 
> e-mails on the basis that the Company is not liable for any such alteration 
> or any consequences thereof.
> Astex Therapeutics Ltd., Registered in England at 436 Cambridge Science Park, 
> Cambridge CB4 0QA under number 3751674
> 

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Re: [ccp4bb] units of f0, f', f''

[Gerard Bricogne]

Dear Ian,

 The iteration seems to be converging :-)) .
 
 Regarding your last paragraph, however, I do not think that we have to
forbid ourselves to call a spade a spade because of possible confusions that
might be caused by misleading abbreviations. If the unit is "an electron's
worth of scattering", its abbreviation to "electron" has to be accompanied
by a suitable annotation so that it does not get confused with some physical
attribute of an electron such as its charge. I don't think that anticipated
inadequacies of notation should stand in the way of correct terminology. If
necessary, we should draft a one-liner that could be added as a footnote to
every Table 1 (like the formula for the R-factor!) and would explain that
the word "electron", as used in the context of that Table, actually means
"an electron's worth of scattering"; and to show how important we are, we
could even have the exact wording reviewed and approved by the Computing
Commission of the IUCr! But this would start sounding like Russian history
in the 1920's ... .


 With best wishes,
 
  Gerard.

--
On Mon, Mar 01, 2010 at 04:14:57PM +, Ian Tickle wrote:
> Dear Gerard
> 
> I would certainly agree that in general, provided one takes sufficient
> care over dimensions and units, paradoxes can never appear.  However,
> in this particular case I was pointing out the dimensionality error of
> writing equations such as "f = 10e", and equivalent ones for the
> structure factor and electron density, given that 'f' is defined as a
> dimensionless ratio (as I believe it usually is).  Even if you
> replaced the 'e' with whatever unit represents an electron's ability
> to scatter X-rays (which would be the amplitude of the scattered
> wave), you still have the same problem.  I only focused on electric
> charge because 'e', the elementary unit of charge, was being posited
> as the unit of 'f'.
> 
> The alternative solution that you suggested of using the word
> 'electron' as an abbreviation for "an electron's worth of scattering",
> is likely to cause just as much confusion and probably would be
> further abbreviated to 'e' anyway, thus leading people to believe it
> represented the electronic charge!  The correct solution, as you, Marc
> and myself have pointed out, is to treat f as a pure number, with
> corresponding treatment of any other quantity that depends on f.
> 
> Cheers
> 
> -- Ian
> 
> 
> On Mon, Mar 1, 2010 at 1:13 PM, Gerard Bricogne  
> wrote:
> > Dear Ian,
> >
> >     Perhaps I should have made a more explicit connection to your message
> > in what I wrote yesterday. I do not think there is any paradox, or apples
> > vs. oranges problem, in this situation.
> >
> >     The structure factor is a count of "electrons as X-ray scatterers", so
> > that the Fourier synthesis computed from them is a number density for these
> > unit scatterers. The density can get clothed with a charge a-posteriori,
> > because we know what the charge of an electron is, but it is not that charge
> > as such that is sensed by the diffraction experiment: it is the complicated
> > combination of charge and mass and various physical constants that ends up
> > determining an electron's ability to scatter X-rays.
> >
> >     I think that if one bears this in mind at all times, paradoxes never
> > appear.

-- 

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Re: [ccp4bb] Deposition of a BUSTER refined structure

[Gerard Bricogne]

Dear Melanie,

 Thank you for your message. You can find the number for the ESD based
on the Luzzati Plot in the REMARK3 section of the header. Several other
coordinate ESD values are listed as well, based on the DPI definitions of
Cruickshank and of Blow. There is a line for the Estimated error of bin free
R value in that same section, but we currently print a value of NULL because
we don't really believe that this can be calculated in a very meaningful way
by any method we are aware of. Perhaps this can be provided at a later
stage.


 Good luck with your deposition!

  Gerard.

--
On Tue, Mar 02, 2010 at 03:09:47PM +, Melanie Vollmar wrote:
> Hi all
> 
> I did my first deposition of a BUSTER refined structure and  I was very
surprised when I was asked for an "estimated error of free R value" and
"estimated error of bin free R value" as well an "ESD based on Luzzati Plot"
during the deposition process.
> 
> I had a detailed look into the refinement log file and I tried the Buster
documentation but I have absolutely no clue where I can find these values.   
> 
> Can someone give me a hint where I can find some information about this or
where the values are in the log file? If they are not listed anywhere, in
which way do they have to be estimated? And what is a Luzzati Plot? I have
never heard of such a plot before... 
> 
> 
> Thank you very much.
> 
> Cheers
> 
> Melanie

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Re: [ccp4bb] Why Do Phases Dominate?

[Gerard Bricogne]

Dear Jacob,

 This is a simple consequence of the convolution theorem, i.e. the
theorem that the Fourier transforms turns a convolution into a product and
conversely.

 As each structure factor (which is a Fourier coefficient) is the
product of a real-valued, non-negative amplitude and of a phase factor (a
complex number of unit modulus), the Fourier transform will turn them into a
map that will be the convolution of the transform of the amplitudes and of
the transform of the phase factors.

 Now, as all the amplitudes are non-negative real numbers, they all have
a phase of zero, so their transform will reach a maximum - and show a huge
dominant peak - at the origin. It will be, so to speak, a "dirty delta
function", with some side-lobes unlike a true delta function, but still very
peaky around the origin. Since the delta function is the unit of convolution
(i.e. the convolution of any function with delta is that function itself),
convoluting the transform of the phase factors with the dirty delta function
coming from the amplitudes will not make much difference to it - therefore
whatever features show up in the electron density map would have been
showing up in the transform of the phase factors in the first place. This is
just another way of saying that "Phases Dominate". This is a crude argument,
assuming for instance a primitive lattice.

 I don't know whether you would call this argument intuitive, but that
is the simplest one I know of.

 There might be other transforms that would emphasise amplitudes, but it
would remain to be seen whether they would produce anything useful if fed
with structure factor amplitudes ... .


 With best wishes,
 
  Gerard.

--
On Thu, Mar 18, 2010 at 12:51:03PM -0500, Jacob Keller wrote:
> Dear Crystallographers,
>
> I have seen many demonstrations of the primacy of phase information for 
> determining the outcome of fourier syntheses, but have not been able to 
> understand intuitively why this is so. Amplitudes as numbers presumably 
> carry at least as much information as phases, or perhaps even more, as 
> phases are limited to 360deg, whereas amplitudes can be anything. Does 
> anybody have a good way to understand this?
>
> One possible answer is "it is the nature of the Fourier Synthesis to 
> emphasize phases." (Which is a pretty unsatisfying answer). But, could 
> there be an alternative summation which emphasizes amplitudes? If so, that 
> might be handy in our field, where we measure amplitudes...
>
> Regards,
>
> Jacob Keller
>
> ***
> Jacob Pearson Keller
> Northwestern University
> Medical Scientist Training Program
> Dallos Laboratory
> F. Searle 1-240
> 2240 Campus Drive
> Evanston IL 60208
> lab: 847.491.2438
> cel: 773.608.9185
> email: j-kell...@northwestern.edu
> ***

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Re: [ccp4bb] Why Do Phases Dominate?

[Gerard Bricogne]

in space.
> >>> Now, you can imagine that when you have many
> >>> wavelets that go up and down, in the average, they
> >>> all cancel and you have a flat surface on a
> >>> body of water in 2D, or, in 3-D, a constant
> >>> density. However, if the wavelet have a certain
> >>> relationship to each other, hence, the mountains
> >>> and valleys of the waves are related, you are able
> >>> to build even higher mountains and even deeper valleys.
> >>> This, however, requires that the wavelets have
> >>> a relationship. They must start from a certain
> >>> point with a certain PHASE so that they are able
> >>> to overlap at another certain point in space to form,
> >>> say, a mountain. Mountains are atomic positions,
> >>> valleys represent free space.
> >>> So, if you know the phase, the condition that
> >>> certain waves overlap in a certain way is sufficient
> >>> to build mountains (and valleys). So, in theory, it
> >>> would not even be necessary to collect the amplitudes
> >>> IF YOU WOULD KNOW the phases. However, to determine the
> >>> phases you need to measure amplitudes to derive the phases
> >>> from them in the well known ways. Having the phase
> >>> you could set the amplitudes all to 1.0 and you
> >>> would still obtain a density of the molecule, that
> >>> is extremely close to the true E-density.
> >>>
> >>> Although I cannot prove it, I have the feeling
> >>> that phases fulfill the Nyquist-Shannon theorem, since they
> >>> carry a sign (+/- 180 deg). Without additional assumptions
> >>> you must do a MULTIPLE isomorphous replacement or
> >>> a MAD experiment to determine a unique phase (to resolve
> >>> the phase ambiguity, and the word multiple is stressed here).
> >>> You need at least 2 heavy atom derivatives.
> >>> This is equivalent to a sampling
> >>> of space with double the frequency as required by
> >>> Nyquist-Shannon's theorem.
> >>>
> >>> Modern approaches use exclusively amplitudes to determine
> >>> phase. You either have to go to very high resolution
> >>> or OVERSAMPLE. Oversampling is not possible with
> >>> crystals, but oversampled data exist at very low
> >>> resolution (in the nm-microm-range). But
> >>> these data clearly show, that also amplitudes carry
> >>> phase information once the Nyquist-Shannon theorem
> >>> is fulfilled (hence when the amplitudes are oversampled).
> >>>
> >>> Best
> >>> Marius
> >>>
> >>>
> >>>
> >>>
> >>>
> >>>
> >>>
> >>> Dr.habil. Marius Schmidt
> >>> Asst. Professor
> >>> University of Wisconsin-Milwaukee
> >>> Department of Physics Room 454
> >>> 1900 E. Kenwood Blvd.
> >>> Milwaukee, WI 53211
> >>>
> >>> phone: +1-414-229-4338
> >>> email: m-schm...@uwm.edu
> >>> http://users.physik.tu-muenchen.de/marius/
> >>
> 
> Dr.habil. Marius Schmidt
> Asst. Professor
> University of Wisconsin-Milwaukee
> Department of Physics Room 454
> 1900 E. Kenwood Blvd.
> Milwaukee, WI 53211
> 
> phone: +1-414-229-4338
> email: m-schm...@uwm.edu
> http://users.physik.tu-muenchen.de/marius/

-- 

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Re: [ccp4bb] Why Do Phases Dominate?

[Gerard Bricogne]

Dear Bart,

 Thank you for further analysing this idea of "inherence", which is so
striking in this case. 

 I just wanted to point out that the most natural setting for Fourier
transform theory is the space L2 of square-integrable functions (although L1
is the more natural one for convolution-related properties). Both of these
are spaces of complex-valued functions from the start, so I am not aware of
a restriction to real-valued functions anywhere in Fourier theory, and no
initial framework thus needs to be broken to accommodate a complex-valued
electron density. Real-valued functions in L1 or L2 are rather oddities, a
little bit like centric reflections for us. Their Fourier transforms have
the extra property of having Hermitian symmetry (the generic mathematical
term for what we call Friedel symmetry). What happens when anomalous
scattering gets us back to a general complex-valued electron density
function is simply that we lose that extra property, not that the framework
of Fourier theory has to be extended.

 This is a minor point, but worth bearing in mind. 


 With best wishes,
 
  Gerard.

--
On Mon, Mar 22, 2010 at 05:00:23PM -0600, Bart Hazes wrote:
> Hi Jabob,
>
> Mathematics is abstract and does not cause anything (well maybe headaches). 
> It describes behaviors of real-world phenomena and probably a lot of other 
> things that have no tangible interpretation.
>
> What Gerard meant when he said that "Fourier transform is at the heart of 
> diffraction" is not that it causes diffraction but that the properties of 
> the Fourier transform form directly capture the properties of the physical 
> phenomenon of diffraction. Unless our understanding of diffraction turns 
> out to be wrong, like the early astronomers were wrong about the center of 
> the universe, the Fourier transform will remain the natural mathematical 
> model for this process.
>
> What does happen frequently is that a simpler mathematical model needs to 
> be replaced by a more general model once more data becomes available. It is 
> conceivable, at least to me, that some day we need a more generalized model 
> for diffraction. For instance, our typical Fourier transforms assume that 
> electron density can be treated as a real value, but heavy atoms also cause 
> a phase shift of the diffracted wave and thus need to be modeled as an 
> imaginary value. That doesn't mean that the initial model was wrong, just 
> that it is only valid in a certain "domain", and outside that domain we 
> need to elaborate the model (which in this case is still a Fourier 
> transform). In many (all?) cases the old model ends up being a special case 
> of the more general variant, just like real numbers are just a special 
> subset of the imaginary numbers.
>
> Bart
>
>
>
> Jacob Keller wrote:
>> - Original Message - From: "Gerard Bricogne" 
>> 
>> To: 
>> Sent: Friday, March 19, 2010 2:32 PM
>> Subject: Re: [ccp4bb] Why Do Phases Dominate?
>>
>>
>>> Dear Marius,
>>>
>>> Thank you for pointing this out - I was about to argue in the same
>>> direction, i.e. that the Fourier transform is at the heart of diffraction
>>> and is not just a convenient, but perhaps renegotiable, procedure for
>>> analysing diffraction data.
>>
>> I wonder how one can establish that a certain mathematical function is "at 
>> the heart" of a phenomenon? Does mathematics cause phenomena, or consitute 
>> the essence of a phenomenon? Many believe that it does, and I am not 
>> saying that I do not feel this way about some relationships between 
>> mathematics and phenomena--but there seems to be a gradation. On one side, 
>> the trajectory of the stream of water from a garden hose is 
>> all-too-obviously essentially a parabola, and on the other side, "laws" 
>> like Moore's law seem completely descriptive and not at all causal or 
>> essential. A gray-area case for me is whether the manifest world is 
>> fundamentally Euclidean, or other such questions. (It certainly *feels* 
>> Euclidean, but...) But what I am unsure about is what standard we use to 
>> decide whether a given phenomenon is *inherently* tied to a given 
>> mathematical function. A troubling thought is that there are many 
>> historical examples of phenomena being *fundamentally* one way 
>> mathematically--and unthinkably otherwise--and later we have revised our 
>> "certainty." One thinks of the example Ian Tickle cited of negative 
>> numbers being meaningless, or also of the Earth's being the center of the 
>> universe and orbits being perfectly circular. A medieval philosopher 
>

Re: [ccp4bb] Help needed in solving a MAD dataset

[Gerard Bricogne]

Dear Qing Lu,

 Now that several suggestions, both ccp4 and non-ccp4, have been made,
may I suggest that you (also) try autoSHARP, available free of charge at 

http://www.globalphasing.com/sharp/

It includes the invocation of SHELXD to solve the substructure, and takes
you all the way to autobuilding with ARP/wARP if you have it installed and
your data resolution is sufficient. It has been around for quite a while and
has many happy users.


 With best wishes,
 
  Gerard.

--
On Wed, May 19, 2010 at 09:06:54AM -0700, Qing Lu wrote:
> Hi All,
> 
> I am new to protein crystallography. I would like to know the steps involved
> in solving a MAD dataset by using the program in CCP4 where you determine
> the phases and then obtain the trace. The dataset is collected at 3
> different wavelengths (peak, inflection and remote) using Se-Met as the
> scatterer. The crystals diffracted to resolution of 2 Angstrsoms and has a
> good anomalous signal.
> 
> Thanks,
> 
> Qing Lu

-- 

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Re: [ccp4bb] Help needed in solving a MAD dataset

[Gerard Bricogne]

Dear Jürgen,

 The road to perfection is a long one ... . Thank you for the feedback!
 
 
 With best wishes,
 
  Gerard.

--
On Thu, May 20, 2010 at 10:31:37PM -0400, Jürgen Bosch wrote:
> I don't like the site finding option in autosharp, takes too long in most of 
> my cases.
> So my approach is locate sites via SHELX, then feed them into Sharp.
> 
> Sorry Gerard :-)
> 
> Jürgen
> 
> On May 20, 2010, at 10:02 PM, Jeremiah Farelli wrote:
> 
> > I second autoSHARP/SHARP.  It makes great initial maps, and once you get it 
> > running, it is totally worth it. 
> 
> -
> Jürgen Bosch
> Johns Hopkins Bloomberg School of Public Health
> Department of Biochemistry & Molecular Biology
> Johns Hopkins Malaria Research Institute
> 615 North Wolfe Street, W8708
> Baltimore, MD 21205
> Phone: +1-410-614-4742
> Lab:  +1-410-614-4894
> Fax:  +1-410-955-3655
> http://web.mac.com/bosch_lab/
> 

-- 

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Re: [ccp4bb] Finding best model for molecular replacement

[Gerard Bricogne]

Dear Paul,

 Thank you for initiating this thread, for so carefully evaluating the
suggestions you received, and for reporting the outcome.

 Your astonishment gives renewed motivation to people who believe it is
still worthwhile continuing to push the frontiers of experimental phasing
and all it entails.

 It would be nice to hear from you again once you have solved your
structure, to find out how you eventually did it.


 With best wishes,
 
  Gerard.

--
On Mon, May 24, 2010 at 04:24:07PM +0200, Paul Lindblom wrote:
> The last molrep job just finished and it found only an odd solution. So I
> think I will try to get my phases elsewhere. But I am somewhat astonished
> that there are still enough cases you can't solve by MR.
> 
> Thanks to all who replied. Here is a list of servers/programs to find a MR
> model:
> 
> http://www.ebi.ac.uk/pdbe-srv/view/
> 
> http://www.ebi.ac.uk/Tools/fasta33/index.html
> 
> http://meta.bioinfo.pl/submit_wizard.pl
> 
> XtalPred
> http://ffas.burnham.org/XtalPred-cgi/xtal.pl
> 
> Balbes  
> http://www.ysbl.york.ac.uk/~fei/balbes/<http://www.ysbl.york.ac.uk/%7Efei/balbes/>
> 
> use the OCA browser for FASTA searches of the PDB
> 
> Modeller or Rosetta (both also available as web servers)
> 
> ensemble of many proteins with Phaser
> 
> FFAS server maintained by the Godzik lab
> 
> generate some models using the "Phyre" server   (
> http://www.sbg.bio.ic.ac.uk/~phyre/
> <http://www.sbg.bio.ic.ac.uk/%7Ephyre/>)  and feed the best .pdbs into
> Mr Bump.

-- 

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Re: [ccp4bb] Heavy atom sites?

[Gerard Bricogne]

Dear Pu,

 If I may add a few remarks those already made by George and Clemens, I
would say that you cannot expect two heavy atom solutions obtained in
separate runs of SHELXD (or any other substructure solution program) from
two distinct sets of differences to be consistent with each other in terms
of origin and enantiomorph - hence the need for checks by cross-difference
Fouriers or (much better) log-likelihood gradient maps for each set of
differences phased by the other. This could get even worse in the case of
polar space groups (e.g. P2(1) ) where a coordinate shift along the polar
axis is left undetermined in each substructure solution. This is a very old
problem - see for instance the method of Bragg ellipses. 

 One way of avoiding this in your case would have been to treat your
isomorphous and anomalous differences jointly by trying to get estimates for
FA values, as if you had a 2-wavelength experiment. This was done under the
old terminology via the Matthews "combined difference Patterson". Then,
solving for your substructure from that combined Patterson would have
produced an automatically consistent solution for both the isomorphous and
the anomalous differences. 

 George: wouldn't XPREP have done that if it had been given the SIRAS
data all at once, instead of separately handling these as SAD and SIR data?


 With best wishes,
 
  Gerard.

--
On Fri, Aug 20, 2010 at 04:32:37PM +0100, Pu Gao wrote:
> Dear all,
> 
> My case seems to have two factors: 1.  origin choice. and 2.  
> handedness/enantiomorph. 
> 
> And this kind of "problem" seems to be very common during the experimental 
> phasing process. And I learned a lot informations both theoretical and 
> practical from your replies. 
> 
> Many thanks for all the replies.  
> 
> Pu

-- 

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 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
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Re: [ccp4bb] Local real-space refinement by phenix

[Gerard Bricogne]

>> On 25 Aug 2010, at 22:17, Pavel Afonine wrote:
>>
>>> On 8/25/10 2:11 PM, George M. Sheldrick wrote:
>>>> I would like to propose that we rename this list to the "Phenix (and
>>>> CCP4) Bulletin Board".
>>>
>>> Sounds too Russian: after collapse of USSR many street names in Moscow, 
>>> as well as metro station names, were renamed back to their "original" 
>>> names they had almost one generation ago (70+ years)  -:)
>>>

 If "70+ years" correspond to "almost one generation ago", Russians must
live very long and have children awfully late! Perhaps this is why they can
accumulate such wisdom ... .
 

 With best wishes,
 
  Gerard.

--

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Re: [ccp4bb] Can CCP4 refine B factors for several residues only?

[Gerard Bricogne]

Dear Pavel,

 I must say that I find some of the statements in your message rather
glib and shallow, especially on the part of a developer. Where is all the
Bayesian wisdom that Phenix is advertised to have absorbed? Your last
paragraph is shocking in this respect. The whole idea of Bayesian inference
is precisely that it isn't good enough to pull out of a hat, by means of a
trick/blackbox, "a" model that corresponds to the data, but that one needs
to see how many models would do fare more or less as well and to give some
rough probability distribution over them; and if your are going to finally
deliver a single model, it had better be as representative as possible of
that weighted ensemble of possible ones, rather than just "a" model that
happens to have been persuaded to fit the data by hook or by crook.

 Closer to practicalities, the procedure by which a model that ends up
being deposited should be reproducible by third parties as the endpoint of a
refinement calculation from the deposited coordinates and X-ray data,
conducted according to the author's description of their own refinement
procedure. That procedure, however, should always end with a justifiable
purely computational step. It seems very dangerous to state that a model in
which some manual moving around of atoms was given the last word is as good
as anything else. If you start encouraging such casual attitudes, you may
end up with 2hr0. 


 With best wishes,
 
  Gerard.

--
On Fri, Aug 27, 2010 at 02:02:48PM -0700, Pavel Afonine wrote:
>  Hello,
>
>>>> The requirement sounds extremely suspect:  every atom in the structure
>>>> contributes to every reflection, so refining "only some atoms" makes as
>>>> little mathematical sense as refining against "only a subset of
>>>> reflections".
>>>>  
>>> I agree with you that the requirement sounds dubious.
>>> But the specific argument you make is not quite right.
>>>
>>> Two common counter-examples are real-space refinement and rigid-body
>>> placement of a known fragment relative to an existing partial model.
>> Not so:  they're tricks to get out of local minima and maybe improve 
>> phases, but they're /not/ useful for generating the model that "best" fits 
>> the data, 
>
> I completely agree with Ethan. Although the overall goal of refining 
> B-factors only for a subset of atoms is not clear (there are at least three 
> example where I do it in phenix.refine - I won't go into technicalities 
> here, it's hidden under the hood and no-one knows -:) ), doing so makes 
> perfect sense in general.
>
>> Or would one deposit a model for which real-space refinement has been the 
>> final step?
>
> Of course you would. Refinement - in whatever space - is just a 
> trick/blackbox to get your model to correspond to the data, and how you do 
> it: in real, reciprocal or both spaces, manually moving atoms or letting 
> minimizer or grid search do that - it does not matter.
>
> Pavel.
>

-- 

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Re: [ccp4bb] Can CCP4 refine B factors for several residues only?

[Gerard Bricogne]

Dear Pavel,

 Yes, I may indeed have been focussed too much attention on your
"subversive"-looking last paragraph, without fully seeing it in the context
of the whole thread. I am also sorry that I was so strident in my criticism:
I should not be writing e-mails on this topic late on a Friday night :-)) . 


 Have a nice weekend.
 
Gerard.

--
On Fri, Aug 27, 2010 at 03:48:03PM -0700, Pavel Afonine wrote:
>  Dear Gerard,
>
> I guess you simply did not understand my email, at all. It's in the 
> archive, you may read it again -:)
>
> All the best!
> Pavel.
>
> P.S. Are you saying people producing (nearly manually) first macromolecular 
> structures BEFORE the era of cool refinement packages were all doing 
> "2hr0"s ? I would stay away from such a strong statements.
>
>
> On 8/27/10 3:35 PM, Gerard Bricogne wrote:
>> Dear Pavel,
>>
>>   I must say that I find some of the statements in your message rather
>> glib and shallow, especially on the part of a developer. Where is all the
>> Bayesian wisdom that Phenix is advertised to have absorbed? Your last
>> paragraph is shocking in this respect. The whole idea of Bayesian 
>> inference
>> is precisely that it isn't good enough to pull out of a hat, by means of a
>> trick/blackbox, "a" model that corresponds to the data, but that one needs
>> to see how many models would do fare more or less as well and to give some
>> rough probability distribution over them; and if your are going to finally
>> deliver a single model, it had better be as representative as possible of
>> that weighted ensemble of possible ones, rather than just "a" model that
>> happens to have been persuaded to fit the data by hook or by crook.
>>
>>   Closer to practicalities, the procedure by which a model that ends 
>> up
>> being deposited should be reproducible by third parties as the endpoint of 
>> a
>> refinement calculation from the deposited coordinates and X-ray data,
>> conducted according to the author's description of their own refinement
>> procedure. That procedure, however, should always end with a justifiable
>> purely computational step. It seems very dangerous to state that a model 
>> in
>> which some manual moving around of atoms was given the last word is as 
>> good
>> as anything else. If you start encouraging such casual attitudes, you may
>> end up with 2hr0.
>>
>>
>>   With best wishes,
>>
>>Gerard.
>>
>> --
>> On Fri, Aug 27, 2010 at 02:02:48PM -0700, Pavel Afonine wrote:
>>>   Hello,
>>>
>>>>>> The requirement sounds extremely suspect:  every atom in the structure
>>>>>> contributes to every reflection, so refining "only some atoms" makes 
>>>>>> as
>>>>>> little mathematical sense as refining against "only a subset of
>>>>>> reflections".
>>>>>>
>>>>> I agree with you that the requirement sounds dubious.
>>>>> But the specific argument you make is not quite right.
>>>>>
>>>>> Two common counter-examples are real-space refinement and rigid-body
>>>>> placement of a known fragment relative to an existing partial model.
>>>> Not so:  they're tricks to get out of local minima and maybe improve
>>>> phases, but they're /not/ useful for generating the model that "best" 
>>>> fits
>>>> the data,
>>> I completely agree with Ethan. Although the overall goal of refining
>>> B-factors only for a subset of atoms is not clear (there are at least 
>>> three
>>> example where I do it in phenix.refine - I won't go into technicalities
>>> here, it's hidden under the hood and no-one knows -:) ), doing so makes
>>> perfect sense in general.
>>>
>>>> Or would one deposit a model for which real-space refinement has been 
>>>> the
>>>> final step?
>>> Of course you would. Refinement - in whatever space - is just a
>>> trick/blackbox to get your model to correspond to the data, and how you 
>>> do
>>> it: in real, reciprocal or both spaces, manually moving atoms or letting
>>> minimizer or grid search do that - it does not matter.
>>>
>>> Pavel.
>>>

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Re: [ccp4bb] process SeMet labelled data

[Gerard Bricogne]

Dear all,

 I wholeheartedly agree with Dirk. I was quite speechless yesterday when
seeing one sarcastic reply after another being sent to this correspondent,
who has probably been put off using this BB ever again. Its purpose is to
help people who need to ask such questions, rather than to serve to display
how clever we are. 


 With best wishes,
 
  Gerard.

--
On Thu, Mar 01, 2007 at 09:08:00AM +0100, Dirk Kostrewa wrote:
> Hi Mark,
> 
> although Shivesh's question was not very specific, and he should have 
> clearly given some more informations about what he would like to know, 
> he is probably a beginner in crystallography and simply asked for help 
> on this board. Not everyone has always time or is always in the mood to 
> answer such questions. In my opinion, it's then better not to respond at 
> all than to give an answer like yours that is neither helpful nor funny! 
> We all should try to keep a good style here.
> 
> Dirk.
> 
> Mark J. van Raaij wrote:
> >why don't you just send all your images to the ccp4bb, then we'll 
> >process them, solve the structure and publish it for you.
> >And we might put you in the acknowledgements, if you are lucky.
> >Mark
> >On 28 Feb 2007, at 16:35, Jonathan Grimes wrote:
> >
> >>Anastassis Perrakis wrote:
> >>>On Feb 28, 2007, at 14:37, shivesh kumar wrote:
> >>>
> >>>>Dear all,
> >>>>I have a data set at 2.2A, of the selenomethionene labelled 
> >>>>protein.How should I process the data.
> >>>
> >>>Carefully !
> >>>
> >>>>Thanx for the help.
> >>>>Shivesh
> >>>
> >>>Tassos
> >>
> >>
> >>  i am sure what tassos really meant was "Very Carefully !"
> >>
> >>  jon
> >>
> >>-- 
> >>Dr. Jonathan M. Grimes,  Royal Society Research FellowUniversity 
> >>Research Lecturer
> >>Division of Structural Biology
> >>Wellcome Trust Centre for Human Genetics
> >>University of Oxford
> >>Roosevelt Drive,
> >>Oxford OX3 7BN, UK
> >>
> >>Email: [EMAIL PROTECTED], Web: www.strubi.ox.ac.uk Tel: (+44) - 
> >>1865 - 287561, FAX: (+44) - 1865 - 287547
> >
> >Mark J. van Raaij
> >Dpto de Bioquímica, Facultad de Farmacia
> >and
> >Unidad de Rayos X, Edificio CACTUS
> >Universidad de Santiago
> >15782 Santiago de Compostela
> >Spain
> >http://web.usc.es/~vanraaij/
> >
> >
> >
> 
> 
> -- 
> 
> 
> Dirk Kostrewa
> Paul Scherrer Institut
> Biomolecular Research, OFLC/110
> CH-5232 Villigen PSI, Switzerland
> Phone:+41-56-310-4722
> Fax:  +41-56-310-5288
> E-mail:   [EMAIL PROTECTED]
> http://sb.web.psi.ch
> 

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Re: [ccp4bb] anisotropic displacement parameter matrix shelxl

[Gerard Bricogne]

Dear Arti,

 The sign | | in this case means "determinant", not "absolute value".
Upon expanding that 3x3 determinant by Cramer's rule you get a cubic
polynomial in lambda, which can indeed be solved by Cardan's formula. You
should definitely give it a try. Condensed algebraic notation like | | can
be confusing.  


 Best of luck,

Gerard.

--
On Sun, Jul 08, 2007 at 01:06:51PM -0600, [EMAIL PROTECTED] wrote:
> Hello all,
> 
> I am trying to understand how the anisotropic displacement parameters
> output by shelxl in the form  U11 U22 U33 U23 U13 U12 relate with the
> displacement in the x, y and z directions of say an ellipsoid in ORTEP.
> So far I tried to find the eigenvalues for the matrix using the relationship
> 
> |Ucart - (lambda)I|=0
> 
> where lambda would give the eigenvalues along the three principal axis. In
> the above relationship, I assumed the | | to stand for absolute value and
> used just basic algebra to find the value of lambda, which will be the
> inverse matrix for Ucart in this case. I used the reference
> 
> On the handling of atomic anisotropic displacement
> parameters
> R. W. Grosse-Kunstleve* and P. D. Adams
> J. Appl. Cryst. (2002). 35, 477±480
> 
> to look up the above relationship. In the paper it is mentioned that
> 
> |Ucart - (lambda)I|=0
> 
> is solved using Cardan's formula.
> 
> So I probably oversimplified my solution and have it wrong.
> 
> Can anyone please help me on this? Is there a simple way of knowing the
> displacement along a major axis on the ellipsoid itself in terms of
> Angstrom?
> Thank you.
> 
> Arti S. Pandey
> Chemistry and Biochemistry
> Montana State University
> Bozeman,MT 59717

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[ccp4bb] LivePDB (related to: The importance of ... )

[Gerard Bricogne]

Dear all,

 It has been quite fascinating to see this thread develop in the past
couple of days, as I was a hair's breadth away from initiating a similar
thread upon returning from the ACA meeting at the end of July.

 An impromptu working dinner was held on the Tuesday evening of the
meeting to discuss various aspects of The Future of the PDB. Most of the
topics that were touched upon were technical, bordering (hardly) on the
clerical. I took advantage of a brief window of opportunity that opened
around the topic of "What should be the PDB's mission" to make a plea for 
precisely the shift of emphasis that has been advocated collectively under
the "Importance of ..." thread: 

 (1) that people should be asked to deposit, and the PDB should archive,
raw images as well as all the information enabling the whole structure
determination and refinement process giving rise to a publication to be
reproduced by any interested third party; this would address the questions
of the reproducibility of results in a fairly radical (and beneficial)
manner; 

 (2) that the existence of such an archive would be enormously
beneficial to the software developers' community, as new developments could
be benchmarked against what was the "state of the art" at the time each 
structure was solved, without the huge effort this involves at the moment;

 (3) that the improvements in methods that such a working practice would
facilitate would themselves contribute to making it possible, in time, to
produce even better results from those annotated raw data than those
originally deposited; in this way, even the contents of the PDB would be
alive and constantly evolving, rather than frozen in their original state;

 I was "surprised and disappointed" (standard euphemism) that the
obvious advantages of such an extension of the PDB's mission were met mostly
with reasons to not do it, with the expected arguments about the volume of
data etc ... . The fact that the PDB is giving its assent to the kind of
initiative that Ashley is talking about is mildly encouraging, but I concur
with others in thinking that this is too important to be left to volunteer
initiatives of this kind in the long run. 


 The side issue of verification and of spotting possible falsification
seems (as others have also mentioned) to be part of a bigger picture, which
is the risk of misbehaviour on the part of anybody who is put under
excessive pressure. Whatever the outcome of this particular incident may
eventually turn out to be, recent hiccups with structures published in
high-impact journals are a sign of a sickness in the system by which the
productivity of scientists is evaluated. We need to find ways of backing off
from this Hollywood-like fascination with (even, addiction to) these
journals, and from the pressure to "publish in Nature or Science, or
perish". I can remember Robert Huber telling me 20 years ago that we should
only publish in real journals, not in "magazines" (as he called Nature) -
and clearly, he had a point. A few years ago, Nature even started organising
conferences on the areas of science it considered as the hottest - a blatant
interference of mecantile media in the internal freedom of judgement of the
scientific community. 


 The two issues (a LivePDB, and the dictatorship of the high-impact
media) are clearly related, in the sense that a LivePDB would be a very
strong basis for calling to account the reviewers and editorial mechanisms
of these journals: this would occur "by default", instead of having to be
triggered by creating such traumatic "causes celebres" as that which emerged
last week.


 With best wishes,
 
  Gerard.


-- 

 ===
 * *
 * Gerard Bricogne [EMAIL PROTECTED]  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
 * *
 ===

Re: [ccp4bb] diffraction images images/jpeg2000

[Gerard Bricogne]

Dear all,

 I think we need to stop and think right here. The errors in pixel
values of images are neither Poisson (i.e. forget about taking square roots)
nor independent. Our ideas about image statistics are already disastrously
poor enough: the last thing we need is to make matters even worse by using
compression methods based on those erroneous statistical arguments!


 With best wishes,
 
  Gerard.

--
On Fri, Aug 24, 2007 at 01:20:29PM +0100, Harry Powell wrote:
> Hi
> 
> Lossy compression should be okay, provided that the errors introduced are 
> smaller than those expected for counting statistics (assuming that the 
> pixels are more-or-less independent) - i.e. less than the square-root of 
> the individual pixel intensities (though I don't see why this can't be 
> extended to the integrated reflection intensities). So it's more important 
> to accurately retain your weak pixel values than your strong ones - an 
> error of ±10 for a pixel in a background count where the background should 
> be 40 is significant, but an error of ±10 for a saturated pixel on most 
> detectors (say, about 64K for a CCD) wouldn't affect anything.
> 
> >On the question of lossy compression, I think we'd have to ask some data
> >reduction guru's how much the "noise" would affect the data reduction. I
> >suspect that the main problem is that the noise added would be
> >correlated across the image and would therefore affect the background
> >statistics in a non-trivial way. Although the intensity measurements may
> >not be badly affected the error estimates on them could be...
> 
> Harry
> -- 
> Dr Harry Powell, MRC Laboratory of Molecular Biology, MRC Centre, Hills
> Road, Cambridge, CB2 2QH


-- 

 =======
 * *
 * Gerard Bricogne [EMAIL PROTECTED]  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
 * *
 ===

Re: [ccp4bb] diffraction images images/jpeg2000

[Gerard Bricogne]

Dear Harry,

 Sorry, this did end up sounding harsher than I intended, and it could
have done with a few judiciously placed smileys :) . My mailer may also have 
been overzealous: there was no intention of bombarding you with disapproval.

 I was simply trying to say that we are still far from fully
understanding the statistics of images, and that if we are to have a chance
of applying future insights into this open question towards improving some
interesting difficult datasets that would have previously been deposited, we
do not want some assumptions to have been made in the compression of the
original images that would, by then, be known to have been erroneous.

 Raw data are sacred. The question is of course: "how raw?"; but the
answer is always going to be to go back to rawer and rawer forms, rather
than towards more and more cooked ones (especially, if the recipes are open
to doubt). 


 With best wishes,
 
  Gerard.


--
On Fri, Aug 24, 2007 at 03:39:31PM +0100, Harry Powell wrote:
> 
> Wow.
> 
> I don't know about the rest of you, but I got told three times.
> 
> Gerard is, of course, right about pixel non-independence (think "point 
> spread function", among other things), and I wouldn't care to argue 
> statistics with him, but as far as I know (and I could well be wrong) most 
> of the integration programs out there _do_ use counting statistics (i.e. 
> Poisson statistics) at least as a first approximation for the random error 
> in measurement; this may be modified by some "detector inefficiency 
> factor" (See Borek, Minor & Otwinowski, Acta Cryst (2003) D59 2031 - 
> 2038), but it's still there and being used by "everyone", nonetheless.
> 
> Having said that, regarding the storage of images, my personal feeling is 
> that there's no real point in using a lossy compression when there are 
> good lossless systems out there. I also think that almost no-one would 
> ever bother to reprocess deposited images anyway; my guess is that 
> "unusual" structures would be detected by other means, and that examining 
> the original images would rarely shed light on the problem.
> 
> >I think we need to stop and think right here. The errors in pixel
> >values of images are neither Poisson (i.e. forget about taking square 
> >roots)
> >nor independent. Our ideas about image statistics are already disastrously
> >poor enough: the last thing we need is to make matters even worse by using
> >compression methods based on those erroneous statistical arguments!
> >
> >
> >With best wishes,
> >
> > Gerard.
> >
> >--
> >On Fri, Aug 24, 2007 at 01:20:29PM +0100, Harry Powell wrote:
> >>Hi
> >>
> >>Lossy compression should be okay, provided that the errors introduced are
> >>smaller than those expected for counting statistics (assuming that the
> >>pixels are more-or-less independent) - i.e. less than the square-root of
> >>the individual pixel intensities (though I don't see why this can't be
> >>extended to the integrated reflection intensities). So it's more important
> >>to accurately retain your weak pixel values than your strong ones - an
> >>error of ±10 for a pixel in a background count where the background 
> >>should
> >>be 40 is significant, but an error of ±10 for a saturated pixel on most
> >>detectors (say, about 64K for a CCD) wouldn't affect anything.
> >>
> >>>On the question of lossy compression, I think we'd have to ask some data
> >>>reduction guru's how much the "noise" would affect the data reduction. I
> >>>suspect that the main problem is that the noise added would be
> >>>correlated across the image and would therefore affect the background
> >>>statistics in a non-trivial way. Although the intensity measurements may
> >>>not be badly affected the error estimates on them could be...
> >>
> >>Harry
> >>--
> >>Dr Harry Powell, MRC Laboratory of Molecular Biology, MRC Centre, Hills
> >>Road, Cambridge, CB2 2QH
> >
> >
> >-- 
> >
> >===
> >* *
> >* Gerard Bricogne [EMAIL PROTECTED]  *
> >* *
> >* Global Phasing Ltd. *
> >* Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
> >* Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
> >* *
> >===
> >
> 
> Harry
> -- 
> Dr Harry Powell, MRC Laboratory of Molecular Biology, MRC Centre, Hills
> Road, Cambridge, CB2 2QH

Re: [ccp4bb] rice stats ref

[Gerard Bricogne]

Dear Bernhard, 

 The title of Rice's paper is "Mathematical Analysis of Random Noise". 
 
 
 With best wishes,
 
  Gerard.

--
On Sun, Nov 11, 2007 at 03:00:10PM -0800, Bernhard Rupp wrote:
> Dear statisticians,
> 
> I wonder if someone might have the section title of the 1954 Rice reference
> 
> Rice SO (1954) in Selected papers on noise and statistics. 
> Wax N (Ed.). New York, NY: Dover Publications. pp 133-195
> 
> I have only 2 pages copied with the function and what seems like
> a piece of the book cover.
> 
> thx, br
> -
> Bernhard Rupp
> 001 (925) 209-7429
> +43 (676) 571-0536
> [EMAIL PROTECTED]
> [EMAIL PROTECTED] 
> http://www.ruppweb.org/ 
> -
> The hard part about playing chicken
> is to know when to flinch
> -

-- 

 ===
     * *
 * Gerard Bricogne [EMAIL PROTECTED]  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
 * *
 ===

Re: [ccp4bb] HKL2000 and gcc4 - redux

[Gerard Bricogne]

Dear Chris,

 Bill just beat me to writing the same. I would mention XDS as well.
 
 
 With best wishes,
 
  Gerard.

--
On Wed, May 07, 2008 at 03:17:07PM -0700, William Scott wrote:
> mosflm is an incredibly great program, not to mention free as in beer...
> 
> 
> 
> 
> On May 7, 2008, at 3:07 PM, Chris Waddling wrote:
> 
> > my frustration at HKL2000 not working

-- 

 ===
 *         *
 * Gerard Bricogne [EMAIL PROTECTED]  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
 * *
 ===

Re: [ccp4bb] Mosflm : data process of crystal with huge unit cell

[Gerard Bricogne]

Dear Francisco,

 It seems that you are encountering the so-called "phi-overlap" problem,
which would be quie acute when your very long c axis gets close to being
parallel to the beam. In this case, even if you are doing fine slicing as
you are doing here with 0.1 degree images, the mosaicity of your crystal may
be enough to cause those overlaps (e.g. between h,k,l and h,k,l+1) within
one image. 

 We had to deal with several instances of this situation in the past
couple of years. The initial images were with the long axis close to
perpendicular to the beam, hence close to parallel to the detector plane.
With those images MOSFLM started with a reasonable value for the mosaicity
(0.6 degree), but as the crystal rotated the "refined" mosaicity drifted
down to unreasonable values, ending up at 0.06 degree so that no overlap was
predicted even with the c axis along the beam! What we had to do was to
manually run spot predictions on the early images with different trial
values of the mosaicity until ALL the spots present, and ONLY the spots
present, were predicted. The optimal value of mosaicity was then given and
kept fixed, leading to the correct detection of phi-overlaps in the late
images and to the correct exclusion of the corresponding reflections from
integration.

 The XDS recipe of assignment of pixels to the nearest reflection in 3D
seems clever, but I do not feel very reassured that it is a robust remedy
for dealing with this special problem. It would be very interesting to know
what you find, when reanalysing your data after your structure is solved,
about the adequacy of that procedure.


 With best wishes,
 
  Gerard.


--
On Thu, May 22, 2008 at 03:47:24PM +0100, [EMAIL PROTECTED] wrote:
> Dear All
> 
> I am processing data from a crystal for a large macromolecular complex
> with mosflm. Cell dimensions are around 120 x 150 x 650, with a p222
> spacegroup. To  avoid overlaps, we have collected data with a oscillation
> of 0.1 degrees.
> 
> When I try to process the data with mosflm, mosaicity decreases along the
> processing to a very low values (0.05 to 0.1 depending on the images). The
> result is that I miss a lot of spots from the images.
> 
> I would appreciate any help regarding :
> 
> 1.- What's is the best strategy to process such a dataset ?
> 2.- Which are the critical parameters in mosflm to avoid these problems,
> and how to modify them ?
> 3.- and finally, can I use this data or your advice is to try to get
> crystals in a different spacegroup ?
> 
> Many thanks
> 
> Best regards
> 
> Francisco
> 
> 
> 
> -
> Francisco J. Enguita, Ph.D.
> Macromolecular Crystallography Laboratory
> ITQB
> EAN, Av. da República
> 2781-901 Oeiras
> Portugal
> Phone : +351-21-4469663
> Fax : +351-21-4433644
> E-mail : [EMAIL PROTECTED]
> -

-- 

 =======
 * *
 * Gerard Bricogne [EMAIL PROTECTED]  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
 * *
 ===

Re: [ccp4bb] Mosflm : data process of crystal with huge unit cell

[Gerard Bricogne]

Dear Francisco,

 With a c axis of 650 Angs your phi-overlap problem is severe. When this
axis is close to being parallel to the beam, the angular distance in radians
between h,k,l and h,k,l+1 for a reflection hkl close to the top or bottom of
an image is the angle spanned by c* viewed at a distance d* (=d*[h,k,l]),
i.e. roughly c*/d*. This gives an angular distance of 1 degree for a c axis
of 180 Angs at a resolution of pi (=3.14159...) Angs. In your case, at a
resolution of 3.25 Angs this angular distance is only 1/200 radian, i.e.
0.286 degree; at higher resolution, it is proportionally smaller. Therefore,
even a small mosaicity (0.2?) will give you severe phi overlap at the top
and bottom of your images (assuming that the spindle axis is horizontal). 

 The best you can hope for is that the estimation of that mosaicity by
matching predicted spots to observed spots will give a correct rejection for
affected reflections - until refinement against measurements that are linear
combinations of intensities of several reflections, rather than intensities
of individual reflections, becomes possible.


 With best wishes,
 
  Gerard.

--
On Thu, May 22, 2008 at 03:47:24PM +0100, [EMAIL PROTECTED] wrote:
> Dear All
> 
> I am processing data from a crystal for a large macromolecular complex
> with mosflm. Cell dimensions are around 120 x 150 x 650, with a p222
> spacegroup. To  avoid overlaps, we have collected data with a oscillation
> of 0.1 degrees.
> 
> When I try to process the data with mosflm, mosaicity decreases along the
> processing to a very low values (0.05 to 0.1 depending on the images). The
> result is that I miss a lot of spots from the images.
> 
> I would appreciate any help regarding :
> 
> 1.- What's is the best strategy to process such a dataset ?
> 2.- Which are the critical parameters in mosflm to avoid these problems,
> and how to modify them ?
> 3.- and finally, can I use this data or your advice is to try to get
> crystals in a different spacegroup ?
> 
> Many thanks
> 
> Best regards
> 
> Francisco
> 
> 
> 
> -
> Francisco J. Enguita, Ph.D.
> Macromolecular Crystallography Laboratory
> ITQB
> EAN, Av. da República
> 2781-901 Oeiras
> Portugal
> Phone : +351-21-4469663
> Fax : +351-21-4433644
> E-mail : [EMAIL PROTECTED]
> -

-- 

 =======
 * *
 * Gerard Bricogne [EMAIL PROTECTED]  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
 * *
 ===

Re: [ccp4bb] buster-tnt on OSX ?

[Gerard Bricogne]

Dear James, 

 I am rather surprised and disappointed to find such an intemperate,
ill-judged and almost slanderous statement from you, especially in a posting
to a bulletin board that is intended for the sharing of experience and good
will and to which you have been such a regular and valued contributor.

 To deal with slander first: Global phasing has been operating for over
10 years without ever being, or intending to be, anyone's chance to "just
try and make a buck". We develop our software thank to a mix of funding that
does include industrial sponsors, but we distribute it free of charge to
academic users (since 2002 we have issued over 3500 licence keys for SHARP
to academic users). We even give support to academic users, and spare no
pains in doing so, as many users can testify: this is not exactly the most
lucrative occupation if one is looking to make a buck. Global Phasing's
staff consists of eight scientists, plus one part-time person to keep the
books and get the annual accounts audited. The company has never had any
investors, and spends all its income on scientists' salaries and running
costs. Perhaps the ".com" suffix has acquired a bad smell in other parts of
the world, but in this case your insinuations are badly misguided.

 If you have had difficulties installing software from us, a more
constructive form of feedback would be to write to us at sharp-develop or
buster-develop (both @globalphasing.com) and explain the nature of those
difficulties. We have often found that the worst problems occur when people,
instead of writing to us, start to try and hack the scripts themselves and
end up tying themselves in inextricable knots. One of your remarks seems to
want to imply that we have taken a perverse pleasure in making installations
difficult. It is true that we still carry a legacy from earlier days when
some of our sponsors wanted to be able to distribute jobs over heterogeneous
clusters of machines and to view the results from any other machine on that
network, while most users today just want to run everything on one machine.
Our installation procedures have kept evolving to become simpler and more
robust, although the need to link up with several third-party packages makes
it hard to suppress complexity entirely. If you happen to have constructive
suggestions to make in this direction, we will be only too happy to listen
to them and will do our best to make use of them. We do have, however, to
weigh up how much time to devote to these issues, vs. how much to developing
and implementing new methods. 

 I hope you will take the time to write to either of the mailing lists I
indicated above to explain what simplifications you would like to see in our
current installation procedures, and look forward to reading them. 


 With best wishes,
 
  Gerard.


--
On Sun, Oct 26, 2008 at 01:40:35AM -0700, James Stroud wrote:
> The info at
>
>   http://www.globalphasing.com/buster/installation/index.html#requirements
>
> will give you some hints about whether it will be successful on OS X. As 
> per the Global Phasing modus operandi, any instruction involving 
> installation of their software is muddled in riddle and ambiguity. They 
> have made an art of making their software difficult to install. I guess the 
> philosophy is that if you can somehow get their software installed, then 
> you have earned your phase information. Personally, I'd rather solve my 
> structure with using chisanbop and a pencil than attempt to install Global 
> Phasing software.
>
> Speaking from experience, this is my 2c. Apologies if I hurt anyone's 
> feelings who are "just trying to make a buck".
>
> James
>
>
>
>
>
> On Oct 24, 2008, at 9:39 AM, jacques-philippe colletier wrote:
>
>> Hi everydoby,
>> I`d like to know if there is a version of BUSTER-TNT available on MacOSX ?
>> Anyone knows ?
>>
>>
>> *
>> Dr. Jacques-Philippe Colletier
>> UCLA / DOE Institute for Genomics and Proteomics
>> 90095 Los Angeles, CA, USA
>> *
>> [EMAIL PROTECTED]
>> [EMAIL PROTECTED]
>> *
>
> --
> James Stroud
> UCLA-DOE Institute for Genomics and Proteomics
> Box 951570
> Los Angeles, CA  90095
>
> http://www.jamesstroud.com

-- 

 ===
 * *
 * Gerard Bricogne [EMAIL PROTECTED]  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
 * *
 ===

Re: [ccp4bb] buster-tnt on OSX ?

[Gerard Bricogne]

Dear James,

 Thank you for your reply. Again, I invite you to share with us the
details of the problems you encountered, through the appropriate mailing
list at Global Phasing.

 I failed, however, to see either humour or constructiveness in your
claim that we were "just trying to make a buck", and could not leave such a
statement hang in the air unanswered.


 With best wishes,
 
  Gerard.

--
On Mon, Oct 27, 2008 at 02:52:16AM -0700, James Stroud wrote:
> Yikes!
>
> Apologies if that was over the top. I guess the chisanbop comment did not 
> properly convey the hyperbole, and hence humor, I was trying to achieve. 
> Hopefully my comments can still be taken as the constructive criticism they 
> were intended to be.
>
> James
>
> On Oct 26, 2008, at 4:57 PM, Gerard Bricogne wrote:
>
>> Dear James,
>>
>> I am rather surprised and disappointed to find such an intemperate,
>> ill-judged and almost slanderous statement from you, especially in a 
>> posting
>> to a bulletin board that is intended for the sharing of experience and 
>> good
>> will and to which you have been such a regular and valued contributor.
>>
>> To deal with slander first: Global phasing has been operating for over
>> 10 years without ever being, or intending to be, anyone's chance to "just
>> try and make a buck". We develop our software thank to a mix of funding 
>> that
>> does include industrial sponsors, but we distribute it free of charge to
>> academic users (since 2002 we have issued over 3500 licence keys for SHARP
>> to academic users). We even give support to academic users, and spare no
>> pains in doing so, as many users can testify: this is not exactly the most
>> lucrative occupation if one is looking to make a buck. Global Phasing's
>> staff consists of eight scientists, plus one part-time person to keep the
>> books and get the annual accounts audited. The company has never had any
>> investors, and spends all its income on scientists' salaries and running
>> costs. Perhaps the ".com" suffix has acquired a bad smell in other parts 
>> of
>> the world, but in this case your insinuations are badly misguided.
>>
>> If you have had difficulties installing software from us, a more
>> constructive form of feedback would be to write to us at sharp-develop or
>> buster-develop (both @globalphasing.com) and explain the nature of those
>> difficulties. We have often found that the worst problems occur when 
>> people,
>> instead of writing to us, start to try and hack the scripts themselves and
>> end up tying themselves in inextricable knots. One of your remarks seems 
>> to
>> want to imply that we have taken a perverse pleasure in making 
>> installations
>> difficult. It is true that we still carry a legacy from earlier days when
>> some of our sponsors wanted to be able to distribute jobs over 
>> heterogeneous
>> clusters of machines and to view the results from any other machine on 
>> that
>> network, while most users today just want to run everything on one 
>> machine.
>> Our installation procedures have kept evolving to become simpler and more
>> robust, although the need to link up with several third-party packages 
>> makes
>> it hard to suppress complexity entirely. If you happen to have 
>> constructive
>> suggestions to make in this direction, we will be only too happy to listen
>> to them and will do our best to make use of them. We do have, however, to
>> weigh up how much time to devote to these issues, vs. how much to 
>> developing
>> and implementing new methods.
>>
>> I hope you will take the time to write to either of the mailing lists 
>> I
>> indicated above to explain what simplifications you would like to see in 
>> our
>> current installation procedures, and look forward to reading them.
>>
>>
>> With best wishes,
>>
>>  Gerard.
>>
>>
>> --
>> On Sun, Oct 26, 2008 at 01:40:35AM -0700, James Stroud wrote:
>>> The info at
>>>
>>>  http://www.globalphasing.com/buster/installation/index.html#requirements
>>>
>>> will give you some hints about whether it will be successful on OS X. As
>>> per the Global Phasing modus operandi, any instruction involving
>>> installation of their software is muddled in riddle and ambiguity. They
>>> have made an art of making their software difficult to install. I guess 
>>> the
>>> philosophy is that if you can somehow get

Re: [ccp4bb] buster-tnt on OSX ?

[Gerard Bricogne]

Dear Jacques-Philippe,

 Sorry to have been distracted into responding to comments on your
question rather than answering your question itself.

 We will shortly be announcing an academic release of a new version of
BUSTER-TNT, which contains several major improvements over the previous one.
It has been under beta-testing since July and has also been made available
to a few academic labs with whom we have a beta-testing arrangement.

 This new version is in the last stages of being ported to MacOSX, but
for the Intel processor only. I hope this release will come in time for your
needs. You are welcome to get in touch for more details through the mailing
list "[EMAIL PROTECTED]" .


 With best wishes,
 
  Gerard.

--
On Fri, Oct 24, 2008 at 09:39:03AM -0700, jacques-philippe colletier wrote:
> Hi everydoby,
> I`d like to know if there is a version of BUSTER-TNT available on MacOSX ?
> Anyone knows ?
>
>
> *
> Dr. Jacques-Philippe Colletier
> UCLA / DOE Institute for Genomics and Proteomics
> 90095 Los Angeles, CA, USA
> *
> [EMAIL PROTECTED]
> [EMAIL PROTECTED]
> *

-- 

 ===
 *     *
 * Gerard Bricogne [EMAIL PROTECTED]  *
 * *
 * Global Phasing Ltd. *
 * Sheraton House, Castle Park Tel: +44-(0)1223-353033 *
 * Cambridge CB3 0AX, UK   Fax: +44-(0)1223-366889 *
 * *
 ===

Re: [ccp4bb] buster-tnt on OSX ?

[Gerard Bricogne]

Dear Pete,

 Thank you for your message. I can confirm that you need not worry about
this clause: it is meant to prohibit the aggressive use of code decompilers
with the intention of stealing the content of the source code. What you have
described in your hypothetical example is nothing of the sort, but instead a
very useful kind of comparative evaluation.


 With best wishes,
 
  Gerard.

--
On Mon, Oct 27, 2008 at 09:53:19AM -0500, Pete Meyer wrote:
> Apologies for going slightly further off-topic...
> 
> Last time I had a free half-day to look into sharp, I noticed that the
> academic license prohibits reverse-engineering.  This seemed to put any
> comparative testing into a slightly grey area.  For example, if I find
> that sharp does the best job refining sites, but bp3 outputs better
> phases for a dataset due to different representation of phase
> probabilities*, I've implicitly constructed a primitive model of how
> sharp is working.  This seems close enough to a first step of
> reverse-engineering that I was concerned.
> 
> Could someone confirm that I'm worrying about things I don't need to here?
> 
> Pete
> 
> * Purely hypothetical example.
> 

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Re: [ccp4bb] phased MR

[Gerard Bricogne]

Dear Tassos,

 I suppose that the "eternal pdb file" you refer to conforms to the
finally agreed standard for the pdb, expected to be valid for the rest of
time ... .

 This clearly shows that SHARP does keep up with the latest and most
forward-looking advances in the field.


 With best wishes,
 
  Gerard.

--
On Tue, Nov 04, 2008 at 01:38:25PM +0100, Anastassis Perrakis wrote:
> Hi -
>
> I would not use mlphare for anything marginal (to be honest not at all).
>
> Both SHARP (use eternal pdb file in top page of the gui) and the new Phaser 
> (look at the doc for scripts for this case) can do what you want.
>
> Tassos
>
>
> On Nov 4, 2008, at 11:55, Thomas Edwards wrote:
>
>> Dear BB,
>>
>> I would like to ask for some advice on phased molecular replacement if 
>> possible.
>>
>> I have a MR model that has so far not proved successful with Phaser, 
>> Molrep, Amore, Beast etc.
>>
>> I have SeMet MAD data to 3.6A that gives decent looking anomalous 
>> difference peaks, looks stable in mlphare, and produces solvent flattened 
>> maps to 2.8A in DM that look like the density might be a sensible shape - 
>> wrt solvent gaps etc - but not interpretable so far (I will be trying 
>> phasing in SHARP, CNS etc).
>> In the mean time, is there a good way to combine phases that may be 
>> slightly sensible with molecular replacement? Things may also be 
>> complicated by the possibility of NCS translations…
>>
>> Any advice gratefully received.
>>
>> Many thanks to all those who continue to provide excellent suggestions,
>> Cheers
>> Ed
>>
>> __
>> T.Edwards Ph.D.
>> Garstang 8.53d
>> Astbury Centre for Structural Molecular Biology
>> University of Leeds, Leeds, LS2 9JT
>> Telephone: 0113 343 3031
>> http://www.bmb.leeds.ac.uk/staff/tae/
>> If you're not part of the solution, you're part of the precipitate. ~Henry 
>> J. Tillman
>>
>>
>

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Re: [ccp4bb] X-Ray versus NMR Structure

[Gerard Bricogne]

Dear Tassos, Bernhard and David,

 If I may push this humourous response (obviously tainted with
crystallographic bias) a little further, I would say that my favourite
mnemonic for the acronym "NMR" is 

  N eeds 
  
  M ore
  
  R esolution
  
 Joking apart, of course, it is a devilishly clever method.


 With best wishes,
 
  Gerard.


--
On Fri, Nov 14, 2008 at 11:28:25AM +0100, Anastassis Perrakis wrote:
> Since I don't like attachments, I will first iterate the title of the 
> attached publication:
>
> "Traditional Biomolecular Structure Determination by NMR Spectroscopy 
> Allows for Major Errors "
>
> It immediately reminded me of an older one (ehm .. one author in common!), 
> addressed at that time mostly to crystallographers:
>
> "Errors in protein structures." (Nature 1996)
>
> ... and I am afraid that the authors were right in both cases (they did not 
> make many friends publishing these though)
>
> Crystallographers learned from that paper back then. And the participation 
> of NMR spectroscopists on the 2006 paper
> implies they are also learning ;-)
>
>   A.
>
> On Nov 14, 2008, at 6:34, Bernhard Rupp wrote:
>
>>> wondering what people think of this.
>>
>> Very funny.
>>
>> But no kidding, Richard Dickerson, the pioneer of DNA crystallography,
>> comes from your institution. For DNA, NMR has the benefit of readily
>> identifying intercalations in short oligomers etc w/o agony of
>> crystallizing.
>>
>> For others, pls see attached. As a physical principle, spectroscopic
>> methods do not deliver atomic resolution structures, but a set of
>> inferences that may or may no be compatible with a molecular model.
>>
>> BR
>> 

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Re: [ccp4bb] Depositing coordinates with riding hydrogens

[Gerard Bricogne]

Dear Ed,

> Riding hydrogens are *not* part of your model, they are part of the
> algorithm used to predict observations.  




 As a diversion from PDB-ology I would point out that, according to
Bayesian statistics, of which the maximum-likelihood method is a rough 
specialisation and approximation, "the model" and "the algorithm used to
predict observations" are identical notions, if the results of that
prediction are understood to be given by probability distributions over
possible observations, and not just as numbers. It is just our habit of
worshipping 3D graven images in the form of PDB files that make us give a
peculiar meaning to the work "model": it is the whole mechanism by which
that file gives rise to a prediction of structure factors (including the
insertion of riding hydrogens, if desired; but also a solvent model and an
error model via the sigmaa parameter) that constitutes "the model" in the
Bayesian sense of the word.

 In any case - it was too good an opportunity to be missed to put a drop
of Bayesian oil into the old crystallographic cogs. 


 With best wishes,
 
  Gerard.

-- 

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Re: [ccp4bb] structure (factor) amplitude

[Gerard Bricogne]

he  
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