AMBER Archive (2005)

Subject: Re: AMBER: substrate exit from protein in Amber 8.0 TI vdw simulation

From: David A. Case (case_at_scripps.edu)
Date: Mon Mar 21 2005 - 12:27:40 CST

On Fri, Mar 18, 2005, Eric Hu wrote:

> Hi, I am trying to perturb a molecule to nothing in a protein binding
> pocket. By looking at the pdb files at the end of each lambda run, the
> molecule has migrated out of the protein when clambda is equal to
> 0.43738 or bigger. One explanation would be that the small molecule
> with shrinking vdw radii do not have favorable interactions with
> protein any more comparing to water molecules and expelled therefore.
> Therefore I wonder if a weak restraint is needed in order to evaluate
> the dV/dL ~ L integral. Thanks.

You will need constraints to keep the ligand from leaving the binding pocket.
See, for example:

%A M.K. Gilson
%A J.A. Given
%A B.L. Bush
%A J.A. McCammon
%T The statistical-thermodynamic basis for compuation of binding affinities:
a critical review
%J Biophys. J.
%V 72
%P 1047-1069
%D 1997

%A J. Hermans
%A L. Wang
%T Inclusion of loss of translational and rotational freedom in theoretical
estimates of free energies of binding. Application to a complex of benzene
and mutant T4 lysozyme
%J J. Am. Chem. Soc.
%V 119
%P 2707-2714
%D 1997

...good luck...dac

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