We tried computing the energy barrier for association / dissociation of a
ligand from an receptor using steered molecular dynamics simulations, thus
taking into account the conformational changes of the protein, but this
method proved to be computationally cumbersome and not very accurate.
You should be able to compute a first order rate constant for LR --> L + R
via MMPBSA, but you will need to reproduce the energy barrier of L-R* via
modeling the system at infinate saturation of L. If you model at infinite
L, then you are modeling the energy of that dissociation barrier. To do
this via simulation using an implicit solvent, you will have to model your
baseline LR structure (i.e., the structure of LR in water), but change the
dielectric of your water (78.4) to that of your ligand / drug.
Sean
----- Original Message -----
From: "David Mobley" <dmobley.gmail.com>
To: <amber.scripps.edu>
Sent: Friday, May 04, 2007 9:41 AM
Subject: Re: AMBER: Rate of Dissociation
> So, you ARE after the rate?
>
> That sounds like a hard problem. You should probably review the
> literature on calculating protein folding rates, as what you're asking
> is related to the question of how one would calculate a protein
> folding rate from a simulation.
>
> David
>
> On 5/4/07, Catein Catherine <askamber23.hotmail.com> wrote:
> > Dear All,
> >
> > Could you please kindly give me some hints if I could calculate the rate
of
> > dissociation of a drug from the receptor protein with AMBER package? If
> > yes, what is the best way to do so?
> >
> > Best regards and many thanks!
> >
> > Cat
> >
> > _________________________________________________________________
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Received on Sun May 06 2007 - 06:07:32 PDT
