So it means we should go on with the Gbind profile not minute details of
fraction decompositions as these fractions do vary and contradict in many
cases whereas Gbind stands tall in majority of cases? But please let me
know if we have a positive decomposition in electrostatic and vry good
overall Gbind above -30kcal/mol then what should we explain on the positive
component of electrostatic contribution? whats does it really signifies and
its correlation with ligand binding?
On Fri, Feb 14, 2014 at 3:13 PM, Jason Swails <jason.swails.gmail.com>wrote:
> On Fri, 2014-02-14 at 08:07 +0200, Soumendranath Bhakat wrote:
> > Dear Community;
> >
> > It is well scripted that binding free leads to funny results which varied
> > publication wise for same complexes in different cases. Also the
> positive a
> > negative contribution in MMPBSA is not well scripted in any Amber
> manual. I
> > believe that Macromodule Embrace calculation from Schrodinger leads to a
> > better binding free compared with ITC than Amber MMPBSA/MMGBSA
> > scripts.Thats a different part and I think work is going on to generate a
> > better binding free profile descriptors.
> > I have some crucial question:
> >
> > What a positive and negative value signifies in the contribution of E
> vdw;
> > E elec, G sol, Ggas ?
>
> Nothing, really. The zero-point energy in force fields is meaningless
> and arbitrary. Only energy differences have any kind of physical
> meaning.
>
> > Will be highly grateful if the community please
> > explain what a positive and negative decomposition on these descriptors
> > stands for and its correlation with Gbind and probable explanation in
> > protein-liagnd binding favourability?
>
> Well certain quantities tend to be strongly correlated -- the Eelec and
> polar solvation free energy (EGB or EPB) tend to cancel each other out
> to a large degree. For the most part force fields are compensatory -- a
> positive vdW is often counteracted by a negative electrostatic
> interaction, for instance, so I would caution against drawing many
> conclusions based on individual components.
>
> Composite components, like Ggas or Gsolv, tend to be a little more
> well-defined physically as they pertain directly to parts of the
> thermodynamic cycle used to define the MM/PB(GB)SA free energy. The
> principle utility of MM/PB(GB)SA analyses are in comparing the full
> binding free energy between related receptors or ligands to maximize the
> cancellation of errors in that comparison.
>
> HTH,
> Jason
>
> --
> Jason M. Swails
> BioMaPS,
> Rutgers University
> Postdoctoral Researcher
>
>
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>
--
Thanks & Regards;
Soumendranath Bhakat
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Received on Fri Feb 14 2014 - 05:30:03 PST
