Re: FEP calculations: defining hybrid residues

From: Jérôme Hénin (
Date: Wed Mar 24 2004 - 11:55:54 CST


Le Mercredi 24 Mars 2004 17:04, Satyavani Vemparala a écrit :
> I am trying to setup systems to compute the relative binding affinities of
> two ligands L1 and L2 to a receptor R.
> In the examples given in the tutorial on NAMD website, the dual topology
> is represented through a hybrid molecule whose residue is defined in the
> RTF file for CHARMM. In this hybrid molecule, there is connectivity
> between initial and final states
> But for my problem, the two ligands L1 and L2 are not connected, in this
> case how do i define a hybrid molecule 'residue' for the CHARMM to
> generate the exclusion lists?

I don't know how you can tell CHARMM to generate exclusions between different
residues. Maybe someone on the list with more experience of that software
than I have will be able to help.
One thing you could do is define a single residue containing both ligands
joined by a "fake" bond with zero force constant. This is rather ugly.

A cleaner approach is to postprocess the PSF file to add the required
exclusions. A happy coincidence is that I'm presently working on a utility
designed to make PSF files suitable for alchemical transformations. I hope to
build a fully functional version next week. It is designed to allow people to
setup alchemical FEP runs without using CHARMM (e.g. using only psfgen), but
it would solve your problem too.


Jérôme Hénin
Equipe Dynamique des Assemblages Membranaires
Université Henri Poincaré / CNRS    UMR 7565
B.P. 239	54506 Vandoeuvre-lès-Nancy Cedex
Tel : (33) 3 83 68 43 95	Fax : (33) 3 83 68 43 71

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