CCL: Assessment of the quality of a Homology Model

 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