Hei Tom,
We may not be able to prevent deposition of dodgy structures, but we could at least give optimal support to those of us wanting to do a good job. With respect to ligands, the support could sometimes be better - thinking in particular of carbohydrate ligands. Best, Ute ________________________________ From: CCP4 bulletin board <[email protected]> on behalf of Tom Peat <[email protected]> Sent: 13 June 2014 09:08 To: [email protected] Subject: Re: [ccp4bb] Hosed-Up X-Ray Structures: A Big Problem I’ll wade into this quagmire before the weekend starts. There are without question some dodgy structures and some of these are due to poor inputs in terms of the cif files that we use for the ligands, or the way we have constructed the ligands, or allowed them to distort during refinement. Some distortions are probably legitimate as maybe you have 1.4 A data and some strain has been introduced, or in fact you put the substrate in and it is partially reacted, so we are seeing an intermediate and that wasn’t taken into account, or some other story. Chemical space is big (really, really BIG) and it is hard to account for all possibilities by just defining each bond type, angle, etc. although we can certainly do better than we have (and in fact I think we are!). And even with everything defined, your mileage will vary (look at all of the safety features we have in cars these days that weren’t there 20 years ago and still thousands die on the road each year). We are really good at protein structures- but if the crystallographer doesn’t look at the data carefully, you get the attached (a recent one that I pulled down that has 1.4 A data and still got this loop wrong- clearly wasn’t looked at very carefully or at all). So, even with really good data, and many automated features, and even good input files, you need the person to actually look at the data and see whether the model fits the density and make a judgement call as to whether the chemistry is plausible and correct. As some people are too busy (or lazy) to do this, there will be structures put into the database which are not only not perfect, but not very good. There are lots of people working on this- PDB REDO, better programs for generating more plausible dictionary files, etc. and they have made our lives much, much easier- Thank You! But all of these won’t eliminate the bad structures deposited (just make it harder to justify a poor structure) unless there is a change in the way structures are deposited (actual criteria for deposition). Do we want that? That is a big question and would really change the dynamics that we currently have. My 2 cents. Cheers, tom From: CCP4 bulletin board [mailto:[email protected]] On Behalf Of Jeffrey Bell Sent: Friday, 13 June 2014 3:05 AM To: [email protected] Subject: Re: [ccp4bb] Hosed-Up X-Ray Structures: A Big Problem Hi, Tim, Thanks for your comment. Do you agree with the editorial's claim that some 25% of the deposited protein-ligand complexes might be dodgy in significant details? This editorial comment represents something that I often hear from drug discovery professionals. Is it a matter of PR between crystallographers and other scientists, or does a real problem exist? Cheers, Jeff Bell PrimeX developer Schrödinger, Inc. On Tuesday, June 10, 2014 10:27 AM, Tim Gruene <[email protected]<mailto:[email protected]>> wrote: -----BEGIN PGP SIGNED MESSAGE----- Hash: SHA1 I hope that the contents of this section is obvious to most readers of the ccp4 bulletin board. Cheer, Tim On 06/10/2014 03:40 PM, Jeffrey Bell wrote: > An editorial comment about protein crystallography appeared under > that title. It's short and worth considering. > http://pipeline.corante.com/ > - -- - -- Dr Tim Gruene Institut fuer anorganische Chemie Tammannstr. 4 D-37077 Goettingen GPG Key ID = A46BEE1A -----BEGIN PGP SIGNATURE----- Version: GnuPG v1.4.12 (GNU/Linux) Comment: Using GnuPG with Icedove - http://www.enigmail.net/ iD8DBQFTlxXkUxlJ7aRr7hoRAlbpAKCcqVkkUwVa2r/M1r9Rp+1rbF6JzgCgiFWR XnSRSZpGKHrDa0tOFgNixJM= =UVlP -----END PGP SIGNATURE-----
