[gmx-users] GPCR/any protein modelling

[K.A. Feenstra]

Chris Shaw wrote:
> 
> Hello All,
> 
> I am attempting to model a GPCR based on the recently reported
> crystal structure of rhodopsin. I have done this and are now
> trying to do some MD on this model. This is where it goes wrong.
> I have tried to do some MD run on the model as with the
> "Getting started tutorial". Short runs in water i.e. 50 ps all
> is fine, however during longer runs i.e. 500 ps (again in
> water) the secondary structure of the model degrades greatly.
> Could anyone help me as to where I am going wrong. ANY HELP
> WOULD BE GREATLY APPRECIATED!!!!

OK, here is any help ;-) ...

I've succesfully ran a series of simulations starting from a homology
model of a cytochrome P450. This was for all practical purposes
perfectly stable. However, I have found that using a series of
energy minimizations (first in vacuum and then with water) and carefully 
selected position restraints (PR) runs (with water) improved the quality
of my model. So, maybe this would be an option for you too.

I did a progression of PR runs, each with more atoms free. First,
only hydrogens could move, then all sidechains (i.e. PR on the backbone).
Then I had a set of residues which, from building the homology model,
were known to be more reliable, which I kept fixed, while releasing
all the rest of the protein. Then as a last step for this reliable set
I only kept backbone atoms fixed. Each successive step was run for
a longer period, staring with 1-10 ps, and the last step was ~100ps.


-- 
Groetjes,

Anton
 ________ ___________________________________________________________
|        | Anton Feenstra                                            |
| .      | Dept. of Pharmacochemistry - Vrije Universiteit Amsterdam |
| |----  | De Boelelaan 1083 - 1081 HV Amsterdam - The Netherlands   |
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| ' __   | Feenstra at chem.vu.nl - http://www.chem.vu.nl/afdelingen/FAR|
|  /  \  |-----------------------------------------------------------|
| (    ) | Dept. of Biophysical Chemistry - University of Groningen  |
|  \__/  | Nijenborgh 4 - 9747 AG Groningen - The Netherlands        |
|   __   | Tel +31 50 363 4327 - Fax +31 50 363 4800                 |
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|        | (Red Hot Chili Peppers)                                   |
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