Dear Piotrek

You can find some info on the use of prior phase information in refinement with 
Refmac in

Acta Crystallogr D Biol 
Crystallogr.<https://www.ncbi.nlm.nih.gov/pubmed/?term=steiner+pannu#> 2011 
Apr;67(Pt 4):355-67. doi: 10.1107/S0907444911001314. Epub 2011 Mar 18.
REFMAC5 for the refinement of macromolecular crystal structures.
Murshudov 
GN<https://www.ncbi.nlm.nih.gov/pubmed/?term=Murshudov%20GN%5BAuthor%5D&cauthor=true&cauthor_uid=21460454>1,
 Skubák 
P<https://www.ncbi.nlm.nih.gov/pubmed/?term=Skub%C3%A1k%20P%5BAuthor%5D&cauthor=true&cauthor_uid=21460454>,
 Lebedev 
AA<https://www.ncbi.nlm.nih.gov/pubmed/?term=Lebedev%20AA%5BAuthor%5D&cauthor=true&cauthor_uid=21460454>,
 Pannu 
NS<https://www.ncbi.nlm.nih.gov/pubmed/?term=Pannu%20NS%5BAuthor%5D&cauthor=true&cauthor_uid=21460454>,
 Steiner 
RA<https://www.ncbi.nlm.nih.gov/pubmed/?term=Steiner%20RA%5BAuthor%5D&cauthor=true&cauthor_uid=21460454>,
 Nicholls 
RA<https://www.ncbi.nlm.nih.gov/pubmed/?term=Nicholls%20RA%5BAuthor%5D&cauthor=true&cauthor_uid=21460454>,
 Winn 
MD<https://www.ncbi.nlm.nih.gov/pubmed/?term=Winn%20MD%5BAuthor%5D&cauthor=true&cauthor_uid=21460454>,
 Long 
F<https://www.ncbi.nlm.nih.gov/pubmed/?term=Long%20F%5BAuthor%5D&cauthor=true&cauthor_uid=21460454>,
 Vagin 
AA<https://www.ncbi.nlm.nih.gov/pubmed/?term=Vagin%20AA%5BAuthor%5D&cauthor=true&cauthor_uid=21460454>.

and references therein.

As stated in the paper (paragraph 2.2.2), the incorporation of prior phase 
information by the refinement function is especially useful in the early and 
middle stages of model building and at all stages of structure solution at 
lower resolutions, owing to the improvement in the observation-to-parameter 
ratio.
Refinement in Refmac is very fast therefore the best thing (as you just did) is 
to try both options and see.

With best wishes
Roberto



On 4 Jan 2019, at 09:55, Piotr Wilk 
<[email protected]<mailto:[email protected]>> wrote:

Dear Eleanor,

I have used the ACORN previously for structure solution but I will have to read 
more about its functionality in structure refinement.
I have run two Refmac jobs using either native or anomalous data with otherwise 
default parameters resulting in R/Rfree of 0.2013/0.2458 and 0.1862/0.2274 
respectively for crystal diffracting to ~1.85A. This seems to me, that using 
anomalous signal in refinement can be useful at least in some cases.

Regards,
              Piotrek


Hmm - you can certainly generate "MAD" phases using the anom signal from one 
data set, and then PARROT or some such density modification tool to extend 
those phases for the higher resolution reflections..
Or ACORN can work well if he data resolution is high enough to give good phases 
for all the data


Then you can use those phases in the initial refinement procedure - the usual 
idea is to use them till the R factor drops below 30% or 35% then just refine 
against the Fobs, phasing just from the model .

But I dont think it is ever worth working at a limited resolution..


Dear Eleanor,

thank you for your comment. My crystals of interest diffract with dmin usually 
between 1.4 and 1.9 A (in high energy data set) and significant anomalous 
signal extends usually to approx. 4 A (in low energy data set).
Certainly I do agree, that in "EITHER, OR" situation one can check both 
approaches, compare the results and take the more convincing one. I can easily 
do that in Refmac running one job against data with Friedel pairs merged and 
parallel one against data with Friedel pairs unmerged. I was considering rather 
an "AND" scenario in which in addition to high resolution data (FP) I'd include 
information from anomalous signal (F+ F-, DANO). I understand that this should 
increase number of observations from a given sample and therefore help to 
refine positions, occupancies and perhaps ADPs for at least a fraction of atoms 
in a model (Mn ions and S in my case). I imagine it as somehow analogical to 
adding geometrical restrains derived from very high resolution data to 
refinement protocols.
I was wondering first of all if my reasoning is sensible and if there is an 
existing protocol to try this?

With kind regards,
                             Piotrek

czw., 3 sty 2019 o 22:00 Eleanor Dodson 
<[email protected]<mailto:[email protected]>> napisał(a):
Hmm - you can certainly generate "MAD" phases using the anom signal from one 
data set, and then PARROT or some such density modification tool to extend 
those phases for the higher resolution reflections..
Or ACORN can work well if he data resolution is high enough to give good phases 
for all the data


Then you can use those phases in the initial refinement procedure - the usual 
idea is to use them till the R factor drops below 30% or 35% then just refine 
against the Fobs, phasing just from the model .

But I dont think it is ever worth working at a limited resolution..

eleanor

On Thu, 3 Jan 2019 at 20:40, Piotr Wilk 
<[email protected]<mailto:[email protected]>> wrote:
Dear Eleanor,

thank you for your comment. My crystals of interest diffract with dmin usually 
between 1.4 and 1.9 A (in high energy data set) and significant anomalous 
signal extends usually to approx. 4 A (in low energy data set).
Certainly I do agree, that in "EITHER, OR" situation one can check both 
approaches, compare the results and take the more convincing one. I can easily 
do that in Refmac running one job against data with Friedel pairs merged and 
parallel one against data with Friedel pairs unmerged. I was considering rather 
an "AND" scenario in which in addition to high resolution data (FP) I'd include 
information from anomalous signal (F+ F-, DANO). I understand that this should 
increase number of observations from a given sample and therefore help to 
refine positions, occupancies and perhaps ADPs for at least a fraction of atoms 
in a model (Mn ions and S in my case). I imagine it as somehow analogical to 
adding geometrical restrains derived from very high resolution data to 
refinement protocols.
I was wondering first of all if my reasoning is sensible and if there is an 
existing protocol to try this?

With kind regards,
                             Piotrek

czw., 3 sty 2019 o 17:02 Eleanor Dodson 
<[email protected]<mailto:[email protected]>> napisał(a):
I think any decision depends on the resolution of your two data sets. If they 
are very different I would choose the higher resolution one.

If that is the Anom data then I would use the anom signal at least in the first 
cycles to improve the phases..

Eleanor

On Thu, 3 Jan 2019 at 14:59, Piotr Wilk 
<[email protected]<mailto:[email protected]>> wrote:
Dear CCP4 experts,

I'd like to ask your opinion about using anomalous signal in refinement of 
crystal structures in addition to using high resolution native data.
I am working on a series of structures for which I have collected two data sets 
(from the same crystal):
1 - native with higher resolution
2 - anomalous at MN absorption edge peak.
The structures were solved with MR and preliminary refinement using the native 
data only yields decent statistics, but I also use anomalous data to verify 
presence and position of manganese ions. For this I used ANODE which lists four 
strong peaks (~30 sigma) as expected for manganese ions and around 45 weaker 
peaks (~9-5 sigma) for sulfur atoms in Cys and Met. I am happy to use this 
information in model building but I was also wondering if (and how) beneficial 
would it be to use both high resolution structure factors and somehow lower 
resolution yet highly specific anomalous signal in the same round of refinement?
In Refmac5 I can use either refinement with "no prior phase information" taking 
FP and SIGFP or "SAD data directly" with SIGFP F(+) SIGF(+) F(-) SIGF(-), but I 
didn't find any "MAD" option to use both.
I have the following columns in my mtz files:
for native data:         H K L FP SIGFP FreeRflag
for anomalous data : H K L FP SIGFP F(+) SIGF(+) F(-) SIGF(-) FreeRflag
or :                           H K L FP SIGFP DANO SIGDANO ISYM FreeRflag

I could use CAD to merge the interesting columns into a single mtz file 
containing:
 H K L FP SIGFP FreeRflag F(+) SIGF(+) F(-) SIGF(-) DANO SIGDANO

I'd appreciate any comments or advise how to use both sources of information in 
the refinement.

I wish you all a Happy New Year.
Kind regards,
                    Piotrek



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Roberto A. Steiner
Professor of Biomolecular Structure
Randall Centre of Cell and Molecular Biophysics
Faculty of Life Sciences and Medicine
King's College London

[email protected]<mailto:[email protected]>
Phone 0044 20 78488216
Fax    0044 20 78486435

Room 3.10A
New Hunt's House
Guy's Campus
SE1 1UL
London


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