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Re: Time for CA-only models to be abolished ? (was: Re: [ccp4bb]: Howto deal with sidechainatoms with low electron density?)
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I fully agree with Gerard in this point. I've immedately signed the NO CA
poll. At least all crystallographers who insist on publishing Fobs should
publish full structures themselves!
Regarding the quality in industry question: I've worked for 8 years as a
crystallographer in a pharmaceutical company in Switzerland with research
departments in Europe and US. During that time we taught our modellers not to
blindly trust coordinates but to inspect electron density maps, which we
started to deposit in-house along with the coordinates. Each crystallographer
was responsible for the quality control of his/her structures, and all wanted
to produce high-quality structures and complexes.
In general, I've noticed a somewhat different approach between European and
US-american industrial crystallographers: in the US a high number of
structures of protein targets with different inhibitors seems to be more
important as the individual and time-consuming refinement of fewer complexes
to a low R/Rfree, but that may have changed.
Best regards,
Dirk.
On Tuesday 26 November 2002 00:25, Gerard DVD Kleywegt wrote:
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>
>
> that's all nice and dandy, but:
>
> (a) what good is information that is unreliable and unverifiable ? is a
> CA-only model with tracing errors really of any use ? is it (biological)
> signal or is it (biological) noise ? i tell students to compare 1PTE and
> 3PTE. then i ask them to have a look at 2PTE ... how much research effort
> and money has gone wasted due to incorrect models we'll probably never
> know.
>
> (b) there are cases of CA-only models with obviously refined temperature
> factors. this suggests that people have 'grep'-ed the CA lines out of their
> PDB file and hence intentionally obfuscated their results.
>
> for a very recent example to which both (a) and (b) apply (plus absence of
> structure factors of course), see FEBS Letters, vol 525, pp 174-175 (2002)
> [plus the reply by the crystallographers on pp 176-178 which, if it wasn't
> so serious a matter, would be laughable]
>
> a question for the industrial crystallographers - how do you address issues
> of quality and reliability ? surely you folks must take this stuff more
> seriously than some of your academic colleagues who demand to be believed
> on the power of their word/reputation/elephantine behaviour ? or am i being
> blue-eyed ?
>
>
> --gerard
>
> On Mon, 25 Nov 2002, Edward Berry wrote:
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> >
> > Gerard DVD Kleywegt wrote:
> > > Speaking of which - isn't it time for a grass-roots movement to root
> > > out that abomination that is CA-only models ?
> >
> > No, I think there is a valid use for CA-only models - when the
> > resolution is 4-5 A and the side chains don't show up but the
> > transmembrane helices do, and the protein is of such importance
> > that the biologists would prefer a TMH + Cofactors model
> > at 5 A to any number of mutant HEW lysozyme structrures at 1.2 A.
> >
> > 2PPS (Photosystem I) was such a case and in my opinion one of the
> > most exciting structures of the last decade. I believe some of the
> > early cryo-EM structures of bacteriorhodopsin were C-a only,
> > and were a huge improvement over the transmembrane-blob
> > structures we had been working with since 1977.
> >
> > It would have cut decades off the time it took for Ron Kaback
> > to solve the structure of lac permease (1M2U) by non-crystallographic,
> > non-NMR means, if he had had a good C-a trace available to
> > thread his structure onto.
> >
> > And the ribosome- even more exciting- surely they don't have
> > side-chains at that resolution. There is an immense amount of
> > useful information in a C-a trace, especially when it shows the
> > juxtaposition of cofactors or nucleic acids and the backbone.
> > For a lot of biologists, the first thing to do when one looks at
> > a structure in RASMOL is to set the display to "backbone" or
> > "ribbons" to see how the thing folds. All those messy side
> > chains just get in the way!
> >
> > Ed
>
> --gerard
>
> ******************************************************************
> Gerard J. Kleywegt
> [Research Fellow of the Royal Swedish Academy of Sciences]
> Dept. of Cell & Molecular Biology University of Uppsala
> Biomedical Centre Box 596
> SE-751 24 Uppsala SWEDEN
>
> http://xray.bmc.uu.se/gerard/ mailto:gerard@xray.bmc.uu.se
> ******************************************************************
> The opinions in this message are fictional. Any similarity
> to actual opinions, living or dead, is purely coincidental.
> ******************************************************************
--
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Dirk Kostrewa
Paul Scherrer Institut
Life Sciences, OSRA/007
CH-5232 Villigen PSI, Switzerland
E-mail: dirk.kostrewa@psi.ch
Phone: +41-56-310-4722
Fax: +41-56-310-4556
WWW: http://www.sb.psi.ch
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