[gmx-users] RE: Gibbs free energy of binding

Ran Friedman ran.friedman at lnu.se
Thu Oct 21 11:16:52 CEST 2010


Under constant pressure a potential energy change is in many cases a good approximation for the change of enthalpy (if only small variations of volume are present). However, for many biomolecular applications, and in particular ligand binding, the entropy contribution cannot be neglected unless you compare two very similar reactions (e.g., delta delta G of binding of two protein inhibitors with similar structures). 

Examples on the size of T delta S are given in many publications discussing MM/PBSA and its variants - in the past we calculated absolute values that were in the same order of magnitude as delta G for a protein-peptide complex (http://dx.doi.org/10.1529/biophysj.106.085399).

I'm not familiar with Material Studio, but there are several methods to calculate entropy changes from MD simulations - quasi harmonic analysis is one that's implemented in Gromacs and Wordom. All have their limitations, but the same is true for experimental measurements of entropy changes upon binding.


Ran Friedman
Biträdande Lektor (Assistant Professor)

Linnaeus University
School of Natural Sciences
391 82 Kalmar, Sweden

+46 480   44 6290 Telephone
+46   76 207 8763 Mobile
ran.friedman at lnu.se
From: gmx-users-bounces at gromacs.org [gmx-users-bounces at gromacs.org] On Behalf Of Ehud Schreiber [schreib at compugen.co.il]
Sent: 21 October 2010 10:39
To: gmx-users at gromacs.org
Subject: [gmx-users] RE: Gibbs free energy of binding

Actually, I believe that using the energy difference, Delta E, as an
approximation to the free energy difference, Delta G, is a valid
approach (which I'm considering myself). The entropic contribution to
Delta G, namely -T Delta S, may be less prominent than Delta E.
In addition, Delta S can be approximated by various means - see e.g.
Doig & Sternberg 1995. I understand that such an approach is utilized in
the Accelrys Discovery Studio.
Obviously, this is an approximation that might be too crude for some

What do you think?


On Oct 21, 2010, at 09:25 , Sander Pronk wrote:

Hi Mohsen,

The mean energy difference is only one component of the free energy

Before you go any further I'd suggest reading a good book on molecular
simulations, like 'Understanding Molecular Simulations' by Frenkel and

There's a good reason free energy calculations cover over half of that


On Oct 21, 2010, at 09:18 , mohsen ramezanpour wrote:

> Dear Justin
> If I do  two  MD simulations for a short time in the same
conditions(of course separately for protein and drug)
>  and calculate total energy of each one and sum them with each other
as E1 as nonbonding free energy of system.
> then a MD simulation for Protein-drug system in the same condition and
calculate it's total energy too as E2 as bound system .
> what does (E1-E2)mean?
> I think it is binding free energy,Is not it?
> in the other hand when we are working on NPT ensamble it means Gibbs
free energy is the main energy and our total energy is equal to Gibbs
free energy.
> Then,what is the problem?
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