[gmx-developers] Intermolecular interactions

[Justin Lemkul]

Hi Devs,

I am working on doing some absolute binding free energy calculations and am 
running into difficulty preserving the orientation of the ligand.  I have tried 
a bunch of things to try to recapitulate the behavior we can achieve in CHARMM 
(e.g. dx.doi.org/10.1021/ci300505n) with intermolecular dihedral and angle 
restraints, but long story short, I haven't found a way to do it.  I need to 
preserve the dihedral between the centers-of-mass of four rings (two in a 
cofactor, two in the inhibitor being annihilated).  Merging the topologies 
didn't work because I can't selectively annihilate the inhibitor unless the 
cofactor is also annihilated, and use of explicit B-state dummy atom types for 
the inhibitor requires manual editing of hundreds of bonded interactions, which 
I don't think is effective.

It seems that there is a patch in Gerrit that has languished for several months 
(https://gerrit.gromacs.org/#/c/2566/) that appears it might do what I need.

I'm happy to provide feedback/testing on that patch if someone (Berk?) can tell 
me if I can use the intermolecular bondeds to set up a dihedral restraint that 
is lambda-dependent (i.e. perturbed as a function of restraint-lambdas in the 
.mdp)?  The pull code works fine to preserve a few translational restraints that 
I need, but the relative orientation is the issue I have.  Simply applying an 
intermolecular dihedral potential would likely also suffice in lieu of a 
restraint if the latter is not possible.

Getting this feature implemented would be a great benefit and I'm happy to be 
the guinea pig for it to get it merged.

Thanks for any insight!

-Justin

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Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

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