AMBER Archive (2008)

Subject: Re: AMBER: For help: how to perform double decoupling thermodynamic integration calculation in AMBER10

From: Thomas Steinbrecher (steinbrt_at_scripps.edu)
Date: Mon Jul 07 2008 - 17:56:49 CDT

Hi yongleli,

you have to break down an absolute binding free energy calculation with
amber into several steps. In one of them, you will decouple the ligand
from its surroundings. That means you will have a prmtop file that
contains the ligand and the solvated receptor, but at lambda=1 the ligand
will behave as if it is in vacuum. In another step, you will close the
circle by reintroducing the ligand into solvent. For these steps, the soft
core potentials introduced in Amber10 are very useful. You also have to
think about applying restraints to your ligand to prevent it from drifting
away out of the binding site at higher lambda values.

Regards,

Dr. Thomas Steinbrecher
The Scripps Research Institute
10550 N. Torrey Pines Rd.
San Diego CA 92037, USA

On Tue, 8 Jul 2008, yongleli wrote:

> Dear Amber Users,
>
> I am trying to calculate absolute binding free energy using termodynamic
> integration with double decoupling method(D. Hamelberg and J. A.
> McCammon, J. Am. Chem. Soc. 126, 7683, 2004). Assume A is a protein
> binding a ligand B,
>
> A:B(sol)-------->A(sol)+B(gas) dG1
>
> In my knowledge of AMBER, In TI calculation there are two prmtop files
> defining initiate state and final state. Here the final state seems to
> be a protein molecule in water and a ligand in vacuum. But I can only
> prepare a parmtop file containing a single protein in water. How can I
> deal with the ligand in gas phase?
>
> I heve also resorted to some papers, just as(S. Wang et. al., J. Am.
> Chem. Soc. 128, 11830, 2006), and (P. Ren et. al., PNAS, 105, 6290,
> 2008), etc. but it seems to that authors did not mention this problem.
>
>
>
> yongleli
> 2008-07-08
>
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