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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Received on Fri Feb 14 2014 - 05:30:03 PST
