[gmx-users] Simulation

[Anton Feenstra]

Sergio Manzetti wrote:
> Hi all, in the past I have had many experiences with MD and the negative 
> effects on protein structures and models. In this regard, I keep certain 
> residues freezed for a better simulation outcome, which highly reduces 
> "negative divergence" from the start model. Believe me, but the start 
> model (if its from protein modelling) can be the best structural 
> candidate all the way to 20% homology and when this is simulated it all 
> becomes worst.

I am just finishing validation of a homology model optimized using MD,
in a method I call 'controlled releas'. I devide the protein in two
parts: binding and non-binding residues. The procedure was as follows,
and indeed provided a better model, for my protein at least:
1) em in vacuum
2) solvate (genbox)
3) em in water
4) MD with constraints on whole protein except sidechains of 'non-binding' res. (~1ps)
5) MD with constraints on whole protein except whole 'non-binding' res. (~10ps)
6) MD with constraints on whole protein except whole 'non-binding' res. and
    sidechains of binding res. (~100ps).
Parameters from procheck were largely unaffected, but dynamical stability
was much improved (RMSD after 1ns went from 0.3 to 0.15 nm), and the
'new' binding cavity had much more specific binding of the substrate.

-- 
Groetjes,

Anton
  _____________ _______________________________________________________
|             |                                                       |
|  _   _  ___,| K. Anton Feenstra                                     |
| / \ / \'| | | Dept. of Pharmacochem. - Vrije Universiteit Amsterdam |
|(   |   )| | | De Boelelaan 1083 - 1081 HV Amsterdam - Netherlands   |
| \_/ \_/ | | | Tel: +31 20 44 47608 - Fax: +31 20 44 47610           |
|             | Feenstra at chem.vu.nl - www.chem.vu.nl/~feenstra/       |
|             | "If You See Me Getting High, Knock Me Down"           |
|             | (Red Hot Chili Peppers)                               |
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