Re: [ccp4bb] To Trim or Not to To Trim

[James Holton]

Follow-up:

My refinements of all possible combinations rotamers are complete. 
Results are remarkably flat!  Be it 10 confomers, 2 conformers, or 
anything in between the correctness of the result, as indicated by 
CCtrue, are all very similar: 0.972 +/- 0.001.  Table below. I define 
CCtrue here as the CC between the ground-truth map and the 2mFo-DFc map 
from a refmac refinement run with default bulk solvent settings.  The 
ground truth is a simulated 7-residue peptide with 10 equally-populated 
whole-molecule conformations, each having ideal geometry and a different 
rotamer for the one Lys side chain.


The biggest drop is between 2 and 1 conformers (case 9 vs 10). It is 23x 
larger than the variation among the first 9 rows. This drop comes from 
the main chain, not the side chain splitting. If the main chain has only 
one conformer, even with all ten side chain rotamers present (case 11), 
the CCtrue is actually worse than having just a stump (12).  
Multi-conformer stumps (13, 14) also fare better than any run with a 
single-conformer main chain (10,11,12), no matter how many side chain 
confs are included. Anisotropic B refinement of one full main& side 
conformer (15) does not do as well as a 2-conf main-chain-only stump 
(13). This is in spite of having a whopping 7-sigma difference peak 
telling you the side chain is missing.


case  CCtrue   Rwork%  Rfree%   fo-fc(sigma)   description
1 0.9699 7.45   11.98  3.1 10 conformers side & main 
together
2 0.9722 6.93   10.60  3.4 9 confs (best of 10 combos)
3 0.9726 6.548.87  3.7 8 confs (best of 45)
4 0.9737 6.548.89  3.7 7 confs (best of 120)
5 0.9736 6.547.88  3.9 6 confs (best of 210)
6 0.9714 7.21   10.60  4.6 5 confs (best of 252)
7 0.9720 6.819.07  4.7 4 confs (best of 210)
8 0.9714 6.749.90  3.5 3 confs (best of 120 combos)
9 0.9720 7.36   10.14  6.8 2 conformers (best of 45 combos)
100.947110.35   15.04  5.2 1 conformer (best of 10 choices)
110.9476 9.66   13.48  4.6 10 confs side, 1 conf main chain
120.9534 9.71   12.12  6.9 stump, 1 conf (best of 10)
130.9665 9.15   11.79  7.0 stump, 2 confs (best of 45)
140.9676 8.75   13.17  6.8 stump, 10 confs
150.9534 8.78   10.82  6.5 stump, 1 conf anisotropic


Now, in my ground-truth model here I did shift the 10 conformers 
randomly relative to each other by rms 0.2 A.  This was to simulate the 
fact that atoms bonded to one another don't really vibrate 
independently. As Helen pointed out earlier, the multi-conformer nature 
of the main chain really does play a role.  Have you ever seen green and 
red blobs on your main chain?  This might be why.


Lijun suggested that perhaps a much larger source of error coming from 
somewhere else could mask this effect, and that is always true.  
However, because errors add in quadrature if the biggest difference 
feature in your map is a side chain you haven't built, then all other 
considerations are secondary. What I hope is apparent here, is the 
unfortunate situation that none of the currently common practices 
actually work very well, even under ideal conditions.


If anyone would like to try different parameters, here is a copy of each 
of these best refinements, as well as a script for generating them all 
from scratch:

https://bl831.als.lbl.gov/~jamesh/trimnotrim/testdata.tgz

-James Holton
MAD Scientist


On 3/19/2023 10:02 PM, Lijun Liu wrote:


Hi James:


First of all, I think all those trim-or-not-to-trim practices are kind 
of compromises when the data did not really offer local density strong 
enough to model side chain reliably. So many smart pioneers could not 
make a simple agreement, which means this science of art has the 
personality-dependent tribute too. Depending on how to interpret(model 
builder) and how to understand (reader), I am ok with a) or c) in your 
list and personally dislike the zero occupancy treatment (sorry if 
this may annoying many ones). The reason is that if a “side chain 
conformation” is modeled with a 0 occupancy, the reading of the 
information turns to be that all other conformations are possible 
(occupancies sums to 1.0) but this modeled one (normally what 
preferred?) which is simply the impossible one for its 0 occupancy and 
particularly mentioned —— logically a paradox.



Your test modeling and refinement of a lysine is interesting, but the 
experiment may not be flawless when trying to compare those different 
strategies. The experiment may be based on a dataset that really 
offers side chain modeling difficulty for its very weak densities 
around the expected location. The huge difference of CCtrue  in your 
experiment probably just means the model’s completeness (4 out of 10 
non-H 

Re: [ccp4bb] is this a real conference?

[Ian Tickle]

Hi Doeke

It's run by a company called Allied Academies:
https://crystallography.alliedacademies.com/2022 whose entry in Wikipedia
is hardly encouraging: https://en.wikipedia.org/wiki/Allied_Academies .
This article gives you a flavour of how they operate:
https://www.chemistryworld.com/news/predatory-conference-scammers-are-getting-smarter/3009263.article
.  The fabricated abstract on the use of "negative mass phlogiston" to
power planes that was apparently unquestioningly accepted by reviewers for
one of their Chemistry conferences (I kid you not) is worthy of an April
Fools (though a little too obvious) !  Basically they just pocket the
exorbitant registration fee.

I think steer well clear is the message!

-- Ian


On Thu, 30 Mar 2023 at 19:04, Doeke Hekstra 
wrote:

> hi everyone,
>
> Just wondering if any of you plan to attend the "2nd International
> Conference on Crystallography, Spectroscopy, and Structural Chemistry”
> scheduled for April 10-12, 2023 in Dubai, UAE. Is it a "real" thing?
>
> I'd ordinarily delete such an email without a thought, but they got me at
> "Exploring New Techniques and Ideas in Crystallography” :)
>
> Best, Doeke
>
> 
>
> To unsubscribe from the CCP4BB list, click the following link:
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>
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[ccp4bb] is this a real conference?

[Doeke Hekstra]

hi everyone,

Just wondering if any of you plan to attend the "2nd International Conference 
on Crystallography, Spectroscopy, and Structural Chemistry” scheduled for April 
10-12, 2023 in Dubai, UAE. Is it a "real" thing?

I'd ordinarily delete such an email without a thought, but they got me at 
"Exploring New Techniques and Ideas in Crystallography” :)

Best, Doeke



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[ccp4bb] Two structural biology postdoc positions availible in the Huber group at the Centre of Medicines Discovery at Oxford University

[Lizbé Koekemoer]

The Huber lab at the Centre for Medicines Discovery (CMD) at the Nuffield
Department of Medicine, University of Oxford, is looking for two highly
motivated and enthusiastic postdoctoral researchers to work with us to
investigate the fundamental role of novel RNA and ubiquitin binding
proteins in human disease.

You will investigate the structural and functional properties of individual
proteins as well as associated complexes involved in RNA and ubiquitin
metabolism. In addition, first-in-class chemical ligands will be designed
in collaboration with academic and pharma partners and characterised in
relevant biochemical assays. There are opportunities to gain experience in
fragment-based drug discovery and join a team of interdisciplinary
researchers.

Applicants are expected to have a strong and demonstrable track record in
protein biochemistry and X-ray crystallography; experience with cryoEM is
highly desirable. Both positions are offered full time on a fixed term
contract for 2 years in the first instance.



Additional details about the posts can be found online:

   1. Job Details (corehr.com)
   

   – closing date: 11-Apr-2023 12:00
   2. Job Details (corehr.com)
   

   – closing date: 26-Apr-2023 12:00 GMT



Interested candidates are welcome to contact Kilian before applying in case
there are any additional questions.



Kilian Huber MRSC

Principal Investigator

Centre for Medicines Discovery



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[ccp4bb] glass capillaries

[Ulrike Demmer]

Dear all,

is anyone still using glass capillaries for crstal mounting  at room 
temperature ???
We have  a couple of them in size from 0.2 - 2.0 mm diameter and 80 mm length.
I would be happy to give them away.

Best,

Ulrike



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