From owner-chemistry@ccl.net Wed Jan 25 02:08:00 2006
From: "Marc Baaden baaden#smplinux.de" <owner-chemistry:-:server.ccl.net>
To: CCL
Subject: CCL: Assessment of the quality of a Homology Model
Message-Id: <-30613-060125015914-10202-NTUNpc5PjXoJlHlL7cdmaA:-:server.ccl.net>
X-Original-From: Marc Baaden <baaden===smplinux.de>
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Date: Wed, 25 Jan 2006 07:10:39 +0100
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Sent to CCL by: Marc Baaden [baaden^_^smplinux.de]

Hi Christofer,

if computing time is not critical, you could use molecular dynamics to
try and distinguish between homology models. For an example comparison
of several quality assessment methods and behaviour in molecular dynamics
simulations, please have a look at [1]. Several experimental structures
and homology models of membrane proteins were taken as a test set there.
I also attach the abstract below.
In particular in some cases MD simulation was able to distinguish between
homology models where the protein quality checkers yielded inconclusive
results.

Regards,
Marc Baaden

[1] Membrane protein structure quality in molecular dynamics simulation
Journal of Molecular Graphics and Modelling, 24 (2005) 157-165
Law, R.J.; Capener, C.; Baaden, M.; Bond, P.J.; Campbell, J.; Patargias, G.;
Arinaminpathy, Y.; Sansom, M.S.P.

Abstract:
Our goal was to assess the relationship between membrane protein
quality, output from protein quality checkers and output from
molecular dynamics (MD) simulations. Membrane transport proteins are
essential for a wide range of cellular processes. Structural features
of integral membrane proteins are still under-explored due to
experimental limitations in structure determination. Computational
techniques can be used to exploit biochemical and medium resolution
structural data, as well as sequence homology to known structures, and
enable us to explore the structure?function relationships in several
transmembrane proteins. The quality of the models produced is vitally
important to obtain reliable predictions. An examination of the
relationship between model stability in molecular dynamics (MD)
simulations derived from RMSD (root mean squared deviation) and
structure quality assessment from various protein quality checkers was
undertaken. The results were compared to membrane protein structures,
solved at various resolution, by either X-ray or electron diffraction
techniques. The checking programs could predict the potential success
of MD in making functional conclusions. MD stability was shown to be a
good indicator for the quality of structures. The quality was also
shown to be dependent on the resolution at which the structures were
determined.


>>> "Christofer Tautermann hannyho*_*yahoo.com" said:
 >> I am builing homology models of proteins (using different programs - e.g. M
     odeller, MOE) by comparative modeling. The output is a huge amount of mode
     ls for the same protein - but the difficulty is to find the "best" structu
     re which is closest to the target. I am using several protein-structure ch
     ecks (WhatCheck, procheck, ...) and they help to discard some unreasonable
      models, but they don't help finding the best model. 
 >> Are there any proposals how to pick the model which is closest to the nativ
     e structure - or at least some of the "better" models?

-- 
 Dr. Marc Baaden  - Institut de Biologie Physico-Chimique, Paris
 mailto:baaden]=[smplinux.de      -      http://www.baaden.ibpc.fr
 FAX: +33 15841 5026  -  Tel: +33 15841 5176  ou  +33 609 843217