From: Blake Charlebois (bdc_at_mie.utoronto.ca)
Date: Thu Sep 02 2004 - 15:31:42 CDT
The following articles may help. I am not sure about the second and third; I
am still working on fully understanding them.
Isralewitz, Gao & Schulten, "Steered molecular dynamics and mechanical
functions of proteins," Current Opinion in Structural Biology, 11:224, 2001
(see sections on biotin/avidin and on analysis)
Jarzynski, "Nonequilibrium Equality for Free Energy Differences," Physical
Review Letters, 78(14):2690, 7 April 1997
Park & Schulten, "Calculating potentials of mean force from steered
molecular dynamics simulations," Journal of Chemical Physics, 120(13):5946,
1 April 2004
From: owner-namd-l_at_ks.uiuc.edu [mailto:owner-namd-l_at_ks.uiuc.edu] On Behalf
Of LEWYN LI
Sent: September 2, 2004 3:27 PM
To: ying xiong
Subject: Re: namd-l: calculate the binding energy or binding free energy?
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?
> $B!!!!!!!!!!!!!!!!(Bying xiong
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)
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,
which is a non-trivial task.
Hope this helps.
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