[Date Prev][Date Next][Thread Prev][Thread Next][Date Index][Thread Index]

Re: [ccp4bb]: homology modelling?



***  For details on how to be removed from this list visit the  ***
***          CCP4 home page http://www.ccp4.ac.uk         ***

On Wednesday 20 November 2002 18:53, Bart Hazes wrote:
> Basically the question is whether current software
> will create a model that is more similar to the real structure than the
> template the model was based on. In the past my (biased?) impression was NO
> and the paper above seems to confirm that. So unless the YASARA force field
> is an acronym for "Your Atomic Structure Always Reliable & Accurate" I
> think modeling should be approached with a properly sceptical attitude. The
> question shouldn't be "what is the easiest way to apply a homologous
> sequence to a known crystal structure" but what is the most accurate method
> and will it be sufficient for the questions you have.
>
> I have been recommending people not to make homology models at all.

Following up on what Bart has said, I've been asked several times recently 
whether or not one should use homology models for molecular replacement, in 
preference to the original crystallographic model with the wrong sequence.  
My (also biased?) impression is that homology modeling makes the models worse 
for molecular replacement, and I have been suggesting that it's probably best 
to stick to the original model, omitting only parts that are clearly very 
different, and perhaps downweighting loops and side-chains that are likely to 
fit poorly (as done in MolRep).

Of course, at some point the techniques of homology modeling will have 
improved enough that the resulting models are actually better when the best 
methods are applied carefully.  So the question is whether we're reaching, or 
even nearing, that point yet.  It would be interesting if people could supply 
clear-cut examples of where homology models were better for molecular 
replacement than the original structures.  Does anybody out there have any 
such examples?  Is my impression still correct, or is it finally out of date?

-- 

Randy J. Read
Department of Haematology, University of Cambridge
Cambridge Institute for Medical Research      Tel: + 44 1223 336500
Wellcome Trust/MRC Building                   Fax: + 44 1223 336827
Hills Road                                    E-mail: rjr27@cam.ac.uk
Cambridge CB2 2XY, U.K.                       www-structmed.cimr.cam.ac.uk