Hi Karl,
Thanks for the reply. Since testing the fitness of each force-field terms
will be time consuming, I fee it could be better to check the role of
temperature on ligand conformation before getting into those QM-MM
calculations. Looking from this aspect, I have a quick query that what
could be the lowest possible temperature where I can do a classical MD
simulation?
Thanks in advance
Regards,
Aneesh
On Tue, Jan 29, 2013 at 9:29 PM, Karl N. Kirschner <
kkirsch.scai.fraunhofer.de> wrote:
> 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 - 22:00:03 PST
