Re: Calculate binding free energy

From: Aron Broom (
Date: Sun Feb 24 2013 - 22:46:17 CST

This is a fairly common topic of research in MD. I would recommend for
initial reading searching for some papers on "MM/PBSA", "Thermodynamic
Integration" and "Umbrella Sampling", which may provide good starting
points on some of the more commonly used techniques.


On Sun, Feb 24, 2013 at 8:22 PM, yp sun <> wrote:

> Dear NAMD users,
> I am now studying how to calculate binding free energy using NAMD. I find
> an answer in namd-I by LEWIN LI as following:
> I presume by "binding (free) energy", you mean that change in
> (free) energy for the following reaction:
> protein (in water) + ligand (in water) ----> protein-ligand complex (in
> water)
> Here is my somewhat naive suggestion:
> I would try to compute the binding energy first by solvating the
> protein-ligand complex in a water box. You would need the x-ray or NMR
> structure of the protein-ligand complex, as well as a box of water
> molecules to do this. Once the system has equilibrated, you could just
> record the total energy. Call it E(P-L).
> Then you can take out the ligand from the protein-ligand complex
> and put the ligand somewhere fairly far away from the protein, in order to
> reduce any interaction between the protein and the ligand. Use a large
> water box if necessary. However, you should make sure that the ligand is
> still inside the water box. You can then re-equilibrate and re-compute
> the total energy. This value will now represent, in an approximate
> way, the total energy of the solvated protein and the solvated ligand.
> Call this E(P + L).
> You can estimate the binding energy simply as:
> E(binding) = E(P-L) - E(P + L)
> I wonder how this method can be realized: how to take out the ligand from
> the protein-ligand complex and put the ligand somewhere fairly far away
> from the protein (using what software)? should the size of the water box be
> the same for calculating E(P-L) and E(P + L)? Should ions be added to
> neutralized both of the two systems?
> Thanks in advance!
> Yeping Sun
> CAS Key Laboratory of Pathogenic Microbiology & Immunology
> NO.1 Beichen West Road,Chaoyang District,Beijing 100101,china

Aron Broom M.Sc
PhD Student
Department of Chemistry
University of Waterloo

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