Comments on: Crystal structure errors — in CSD too http://www.simbiosys.com/blog/2008/06/13/crystal-structure-errors-in-csd-too/ Addressing the challenges of computational drug discovery Thu, 09 Feb 2012 21:51:18 +0000 http://wordpress.org/?v=2.0.11 by: ChemSpider Blog » Blog Archive » When a Scientific Blog Posting, Data Licensing and Open Data Access Come Together http://www.simbiosys.com/blog/2008/06/13/crystal-structure-errors-in-csd-too/#comment-1493 Thu, 19 Jun 2008 12:37:05 +0000 http://www.simbiosys.com/blog/2008/06/13/crystal-structure-errors-in-csd-too/#comment-1493 [...] The past couple of days has seen an interesting exchange going on over on the SimBioSys blog. Zsolt Zsoldos is someone I respect, not only for his passion for his science but also for his want to educate others in the challenges of what he does in developing software. I believe his blog post entitled “Crystal Structure Errors in CSD too” was an honest attempt to tell people to be “careful” when using data from databases. I don’t care whether the database is ChemSpider, PubChem, the CAS Registry or any of the other databases available via free access of commercial transaction, they ALL have errors. It is inevitable. Zsolt’s attempt to highlight that such errors exist was done, I believe, with pedagogical intent. [...] […] The past couple of days has seen an interesting exchange going on over on the SimBioSys blog. Zsolt Zsoldos is someone I respect, not only for his passion for his science but also for his want to educate others in the challenges of what he does in developing software. I believe his blog post entitled “Crystal Structure Errors in CSD too” was an honest attempt to tell people to be “careful” when using data from databases. I don’t care whether the database is ChemSpider, PubChem, the CAS Registry or any of the other databases available via free access of commercial transaction, they ALL have errors. It is inevitable. Zsolt’s attempt to highlight that such errors exist was done, I believe, with pedagogical intent. […]

]]> by: J http://www.simbiosys.com/blog/2008/06/13/crystal-structure-errors-in-csd-too/#comment-1491 Mon, 16 Jun 2008 13:39:18 +0000 http://www.simbiosys.com/blog/2008/06/13/crystal-structure-errors-in-csd-too/#comment-1491 These comments are interesting - not because they reveal anything that a small molecule crystallographer doesn't know: More because they reveal that modellers have expectations of information that are a bit naive. I'm a long time user of the CSD and, as a small molecule crystallographer, I understand the caveats behind crystallographic data. There are errors in the published crystal structures, and not all of them will get spotted during peer review or data curation. CSD users would be well advised to try to understand them and factor them in to their work. I particularly turn your attention to Points 3 and 4 below ... Point 1. H-positions are sometimes hard to resolve in small molecule studies, and need to be treated warily in crystal structures. Ok - the entry QUICNA01 is a neutron study, so one would expect them to be better, but disordering is an issue. One should always look at both the 2D and 3D structural information when working with crystal structures. If you look at the 2D representation in the CSD for QUICNA01 it is correct. Point 2. Undiagnosed disorder/symmetry can lead to problems: There are structural studies in the CSD where the crystallographer has missed a disorder, or missed some symmetry. AACRUB is an example of missed symmetry - and when you look at the study you see rather dubious bond lengths and angles, due to correlations in the refinement co-variance matrix. Quite often, when this sort of thing happens, a later study will then correct the error: see AACRUB01 in this case. Missed dis-orderings and symmetry are hard to spot, note: This is by far the most likely thing to trip up a modeller who 'just wants the coordinates'. Point 3. Newer structural studies are more likely to be more reliable than older studies due to enormous improvements in equipment and software to undertake the studies. I think, in the case of QUICNA01 this is very pertinent. The structure was published in 1974 .... Ok - if this is the only structure then you may have to use it but .... Point 4. If there are several similar studies of a structure, they end up in a CSD refcode family. In the case of QUICNA01 you also have some later studies - namely QUICNA02 QUICNA03 QUICNA10 QUICNA11 QUICNA12 QUICNA13 QUICNA10, QUICNA11, QUICNA12 and QUICNA13 are all later studies of the structure, and they *all* have the proton to which you refer, since they are 'deuterated' compounds which will resolve better in neutron studies. Now - you might quite reasonably say 'but how do I know which one to pick?' - There is this study http://www.ccdc.cam.ac.uk/free_services/best_representative/ Though admittedly for QUICNA note that the choice is inconclusive based on the 4 lists given: I think the hydrogen list may not account for deuteration. These comments are interesting - not because they reveal anything that a small molecule crystallographer doesn’t know: More because they reveal that modellers have expectations of information that are a bit naive.

I’m a long time user of the CSD and, as a small molecule crystallographer, I understand the caveats behind crystallographic data. There are errors in the published crystal structures, and not all of them will get spotted during peer review or data curation. CSD users would be well advised to try to understand them and factor them in to their work. I particularly turn your attention to Points 3 and 4 below …

Point 1.

H-positions are sometimes hard to resolve in small molecule studies, and need to be treated warily in crystal structures. Ok - the entry QUICNA01 is a neutron study, so one would expect them to be better, but disordering is an issue.

One should always look at both the 2D and 3D structural information when working with crystal structures. If you look at the 2D representation in the CSD for QUICNA01 it is correct.

Point 2.

Undiagnosed disorder/symmetry can lead to problems: There are structural studies in the CSD where the crystallographer has missed a disorder, or missed some symmetry. AACRUB is an example of missed symmetry - and when you look at the study you see rather dubious bond lengths and angles, due to correlations in the refinement co-variance matrix.

Quite often, when this sort of thing happens, a later study will then correct the error: see AACRUB01 in this case.

Missed dis-orderings and symmetry are hard to spot, note: This is by far the most likely thing to trip up a modeller who ‘just wants the coordinates’.

Point 3.

Newer structural studies are more likely to be more reliable than older studies due to enormous improvements in equipment and software to undertake the studies. I think, in the case of QUICNA01 this is very pertinent. The structure was published in 1974 …. Ok - if this is the only structure then you may have to use it but ….

Point 4.

If there are several similar studies of a structure, they end up in a CSD refcode family. In the case of QUICNA01 you also have some later studies - namely QUICNA02 QUICNA03 QUICNA10 QUICNA11 QUICNA12 QUICNA13

QUICNA10, QUICNA11, QUICNA12 and QUICNA13 are all later studies of the structure, and they *all* have the proton to which you refer, since they are ‘deuterated’ compounds which will resolve better in neutron studies.

Now - you might quite reasonably say ‘but how do I know which one to pick?’ - There is this study

http://www.ccdc.cam.ac.uk/free_services/best_representative/

Though admittedly for QUICNA note that the choice is inconclusive based on the 4 lists given: I think the hydrogen list may not account for deuteration.

]]> by: Ashutosh http://www.simbiosys.com/blog/2008/06/13/crystal-structure-errors-in-csd-too/#comment-1490 Sat, 14 Jun 2008 06:12:15 +0000 http://www.simbiosys.com/blog/2008/06/13/crystal-structure-errors-in-csd-too/#comment-1490 Gerhard Kleywegt is a very entertaining and funny speaker. His recent talk at an OpenEye meeting was both hilarious and informative. It's good to be mindful of errors in crystal structures as you indicated. While you note correctly that x-ray structures should not be too far from the global minimum, since global minima are force-field dependent, it's hard to judge exactly how far they are from the solution global minimum. Plus, gas phase force-field global minima are often compromised and overstabilized by electrostatic interactions. Gerhard Kleywegt is a very entertaining and funny speaker. His recent talk at an OpenEye meeting was both hilarious and informative. It’s good to be mindful of errors in crystal structures as you indicated. While you note correctly that x-ray structures should not be too far from the global minimum, since global minima are force-field dependent, it’s hard to judge exactly how far they are from the solution global minimum. Plus, gas phase force-field global minima are often compromised and overstabilized by electrostatic interactions.

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