Hi Aneesh,
It is difficult to say if your simulations went wrong or not. For one, maybe your ligand is sampling conformations that are appropriate for a room temperature solution-phase model (assuming that is what you are doing). The crystal structure was likely solved at a much lower temperature, resulting in the preferred conformation you see in the PDB file.
With that said, one could investigate how well the different force-field terms that you are using perform at reproducing known experimental observables in analogues, if available. Alternatively you could see how they reproduce QM-generated rotational curves for that molecule or a smaller analogue. Doing so may provide you some confidence in their use in MD simulations. (Be forewarned, this can be time consuming to accomplish.)
Best regards,
Karl
----- Original Message -----
From: "aneesh cna" <aneeshcna.gmail.com>
To: "AMBER Mailing List" <amber.ambermd.org>
Sent: Tuesday, January 29, 2013 2:12:38 PM
Subject: [AMBER] Fwd: Regarding the problem with ligand conformation
Dear Amber users,
I am working with the protein-ligand systems. The protein-ligand complex
structure was obtained from Protein Data Bank. Before starting the
simulation, I have carried out QM calculation ( b3lyp/6-311+g* ) of ligand
to get the optimized structure and ESP fitted point charge for the atoms.
The optimized ligand geometry was similar to the crystal structure. Then, I
have used the antechamber module of Amber to prepare the parameter file (
PREP and FRCMOD files) for the ligand, where I used the GAFF force field.
Unfortunately, the ligand geometry has been changed drastically during the
initial stages of production run ( after ~1ns of equilibration phase) of
simulation. The ligand keep its proper conformation ( i.e. close to
crystal conformation) for the initial ~1 ns phase of equilibration. Is it a
problem with force field? . If so ( i.e., if there is any problem with
ligand FF parameters), the observed conformational changes should happen in
the initial stage of the simulation rather than at the end of ~1ns
equilibration.
Can anyone help me to figure out what went wrong with my simulation.
I have attached three snapshot of the ligand (crystal structure, QM
optimized, after equilibration respectively), for your reference.
Thanks in advance
Sincerely
Aneesh
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Received on Tue Jan 29 2013 - 08:00:03 PST
