Hello Aneesh,
I have been thinking about your problem some, and I am curious about the performance of the parameters within your ligand. Could you send an image of your molecule with the atom type definition labeled next to the corresponding atom? (I assume you used parmchk after running antechamber to supply any missing parameters, correct?).
Cheers,
Karl
----- Original Message -----
From: "aneesh cna" <aneeshcna.gmail.com>
To: "AMBER Mailing List" <amber.ambermd.org>
Sent: Wednesday, January 30, 2013 8:22:33 AM
Subject: Re: [AMBER] Fwd: Regarding the problem with ligand conformation
I maintain the system tepmerature at 300K. As Karl suggested, to see there
is any effect of temperature on ligand conformation, I would like to try
out few simulations possibly in the range of 283K - 293K.
On Wed, Jan 30, 2013 at 11:31 AM, Bill Ross <ross.cgl.ucsf.edu> wrote:
> > what
> > could be the lowest possible temperature where I can do a classical MD
> > simulation?
>
> What would be your ideal?
>
>
> Bill
>
> aneesh cna <aneeshcna.gmail.com> wrote:
>
> > 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 Thu Jan 31 2013 - 01:30:03 PST
