Equilibrate the system properly and run 4 different MD s with different
initial velocities and perform either GBSA or PBSA calculation and check if
this problem stays there or not. Or you can check framewise calculation of
MM/GBSA or MM/PBSa over the time to check if its changing or same. If
binding free energies are too positive (unfavorable), the ligand
sterically clashes to some degree with the protein. Search literatures and
you can find examples of positive contribution of MM/GBSA and possible
explanation.
HTH!
SB
On Wed, Jul 2, 2014 at 1:55 PM, David A Case <case.biomaps.rutgers.edu>
wrote:
> On Wed, Jul 02, 2014, Zeinab Tavasoli wrote:
> >
> > I am performing free energy calculation with MM-PBSA.py for a crystal
> > structure of a protein-ligand complex.
> >
> > Although I have checked the structure of the complex after production
> and I
> > am sure about the binding of ligand to its proper site, ΔG value is
> > positive.
>
> > I don't know where to look for the origin of this problem.
>
> There could be many, many reasons for such a result. Errors can arise
> from a
> poor force field, from lack of good equilibration, from the assumption of a
> single trajectory model, or from the limitations of the implicit solvent
> models used in the MM/PBSA model, or from problems with estimating
> configurational entropies. Figuring this out is not something that is
> easily
> "solved" on a mailing list--it is not even clear that there is a problem
> to be
> solved.
>
> ....dac
>
>
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>
--
Thanks & Regards;
Soumendranath Bhakat
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Received on Wed Jul 02 2014 - 05:30:02 PDT
