Calculate binding free energy

From: yp sun (
Date: Sun Feb 24 2013 - 19:22:08 CST

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 
         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

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