From: Philip Fowler (
Date: Thu May 12 2005 - 04:37:31 CDT

We have also been using the FEP module with NAMD2.5 and agree that a soft-core
potential would help enormously. I am also interested in the possibility that
it may allow one to assess when a lambda simulation has "relaxed" - I
hestitate to say equilibrated (Yang et al. J Chem Phys 120 2618 (2004)).

At UCL we have briefly looked at implementing it, but currently do not have
anyone free to do it. Is anyone on the list implementing it (or would be
tempted to give it a go?).

Wei - are you introducing a charge into your system, and if so, how are you
dealing with this (e.g. scaling an ion also)?

--Phil Fowler

> There is, indeed, a singularity when lambda tends towards
> 0 or 1 with growing particles - known as "end-point"
> catastrophe. One way to circumvent this difficulty is to
> use a soft-core potential in the spirit of Beutler et al.
> Chem. Phys. Lett. 1994, 222, 529-539. Unfortunately, we
> have not implemented it yet in NAMD. A work-around that you
> might want to try is to use windows of uneven width, getting
> infinitesimal as you approach the end points of the reaction
> path. In addition, you may want to equilibrate and start at
> lambda = 0.5, and move in both directions, towards 0 and 1,
> to avoid poor vdW contacts due to growing atoms (note that,
> strictly speaking, in the dual-topology paradigm, we scale
> the interaction potential energy with lambda rather than the
> non-bonded parameters of the appearing/disappearing side chains).
> Chris Chipot
> Wei Chen wrote:
> >Hi, all,
> >
> >Now I am using free energy perturbation to calculate free energy
> > difference. The system is one ligand + one receptor. I want to mutate one
> >residue in binding pocket from Glycine to Aspartate.
> >
> >Basically, I grow aspartate and shrink glycine at the same time.
> >The problem is that aspartate could overlap with other residues due
> >to its bigger size than glycine. So the VDW energy becomes very large,
> >even infinite. Anybody has ideas to deal with this situation?
> >
> >Thanks!
> >
> >Wei Chen
> _______________________________________________________________________
> Chris Chipot, Ph.D.
> Equipe de dynamique des assemblages membranaires
> Unité mixte de recherche CNRS/UHP No 7565
> Université Henri Poincaré - Nancy 1 Phone: (33) 3-83-68-40-97
> B.P. 239 Fax: (33) 3-83-68-43-87
> 54506 Vandoeuvre-lès-Nancy Cedex
> E-mail:
> To sin by silence when we should protest makes cowards out of men
> Ella Wheeler Wilcox
> _______________________________________________________________________

Philip Fowler, 
PhD Student
Centre for Computational Science,
UCL Chemistry

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