Re: [AMBER] MMPBSA Results

From: Jason Swails <>
Date: Thu, 19 May 2016 08:22:13 -0400

On Thu, May 19, 2016 at 5:19 AM, asdda asa <> wrote:

> Dear Amber users,
> I calculate binding free energies of a series of ligand-protein complexes
> using MM-PBSA, and the results show that the electrostatic energy
> components (Δ*E*ELE) were positive for all complexes, while the polar
> energies of desolvation (Δ*E*PBCAL) were all negative.
> Please, what can be inferred from the data.
> Previously I did the MM-PBSA calculation for different ligand-protein
> complexes, and the electrostatic energy components were all negatives,
> while the polar energies of desolvation were all positives.

To me it implies that electrostatic interactions between the ligand and
receptor are favorable. For example, partially negative groups on the
ligand interact with partially positive groups on the receptor (or vice
versa), so that when you *remove* those interactions the electrostatic
energies of the unbound species is larger than the electrostatic energies
of the bound species (since it is missing the stabilizing interactions
between the receptor and ligand in the unbound state, obviously).

​But those charge/charge interactions don't just disappear when the complex
breaks apart, they are replaced by interactions with water. So while the
loss of electrostatic stabilization in the unbound state results in a
positive electrostatic binding contribution, the charged active site and
ligand are more easily solvated, so the polar solvation contribution will
be negative.

This is a common theme -- solvation and electrostatics typically offset
(for that precise reason).


Jason M. Swails
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Received on Thu May 19 2016 - 05:30:06 PDT
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