Re: [AMBER] calculating absolute binding free energy using MMPBSA

From: Jason Swails <>
Date: Wed, 04 Jun 2014 07:55:57 -0400

On Wed, 2014-06-04 at 02:17 -0700, menwer momo wrote:
> Dear amber users,
> I used mm-pbsa to calculate the binding free energy of a protein-DNA complex,
> Is the PBTOT given as the out put of this is the relative binding free
> energy?
> If I want to calculate the absolute binding free energy ( in order to
> compare it with the experimental value) should I subtract T∆ S
> (calculated using normal mode analysis) from PBTOT ?

If you want an absolute free energy, then yes, you will need to somehow
include solute entropy.

If you want that absolute free energy to be even remotely reliable,
however, you have two choices:

1) Investigate the literature to see how people have modified the
standard MM-PBSA protocol in order to get more accurate absolute free
energy estimates. The papers from the Ryde group is a good place to

2) Use another method (like TI)

Absolute binding free energies from the standard MM/PBSA protocol are
wholly unreliable (if they are accurate, I would consider that a
fortunate accident). Computing accurate absolute free energies of
binding is still a very challenging task for which there is no method
that is both fast (like MM/PBSA) and accurate (like TI).


Jason M. Swails
Rutgers University
Postdoctoral Researcher
AMBER mailing list
Received on Wed Jun 04 2014 - 05:00:04 PDT
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