# Re: calculate the binding energy or binding free energy?

From: LEWYN LI (ll2150_at_columbia.edu)
Date: Thu Sep 02 2004 - 14:27:03 CDT

On Thu, 2 Sep 2004, ying xiong wrote:

> Dear sir,
> Could you please tell me whether NAMD program can calculate the bind
> energy or binding free energy of protein and ligand ? If yes, how to
> calculate it?
>
>
> 　　　　　　　　ying xiong
> 　　　　　　　　yxiong_at_mail.ccnu.edu.cn
> 　　　　　　　　　　2004-09-02

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)

Of course, this estimate may or may not be close to experiments,
because, in experiment, you usually determine the equilibrium constant and
then calculate the binding FREE energy as dG = -RTlnK.

I think the binding free energy is more complicated to calculate,
because you would need to determine the change in entropy of binding,