I sense someone should quickly point out, on behalf of the developers (I
assume it's they that are requested to magically "give optimal
support"), that it's not for want of awareness, intelligence or
diligence that this functions are suboptimal: it's want of TIME. As
Paul suggested, in ccp4 alone there are several active projects on
carbohydrates, nucleic acids, and general restraints.
And it's not as if the tools to do this aren't available: defining
custom restraints has been possible for ages. It's just not as
fantastically convenient as everything else.
The fact that /these/ errors are now becoming prominent is testament to
how excellent the /rest/ of our toolset has become... presumably the
reason we've become too lazy to look at our restraints in detail,
because to be honest, few /other /aspects of the analysis require such
detailed attention. Now THAT's what I call impressive.
phx.
P.S. The first "C" in CCP4 stands for "Collaborative", i.e. anybody with
good ideas is welcome to contribute the tools they write into the mix...
On 13/06/2014 08:43, Ute Krengel wrote:
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/
<http://www.enigmail.net/>
iD8DBQFTlxXkUxlJ7aRr7hoRAlbpAKCcqVkkUwVa2r/M1r9Rp+1rbF6JzgCgiFWR
XnSRSZpGKHrDa0tOFgNixJM=
=UVlP
-----END PGP SIGNATURE-----
