<div dir="ltr">Hi,<div><br></div><div>The patch Justin mentions seems to work and is likely to be in 5.1</div><div><br></div><div>Mark</div></div><br><div class="gmail_quote"><div dir="ltr">On Sun, Jun 14, 2015 at 4:04 PM Justin Lemkul <<a href="mailto:jalemkul@vt.edu">jalemkul@vt.edu</a>> wrote:<br></div><blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex"><br>
Hi Devs,<br>
<br>
I am working on doing some absolute binding free energy calculations and am<br>
running into difficulty preserving the orientation of the ligand. I have tried<br>
a bunch of things to try to recapitulate the behavior we can achieve in CHARMM<br>
(e.g. <a href="http://dx.doi.org/10.1021/ci300505n" rel="noreferrer" target="_blank">dx.doi.org/10.1021/ci300505n</a>) with intermolecular dihedral and angle<br>
restraints, but long story short, I haven't found a way to do it. I need to<br>
preserve the dihedral between the centers-of-mass of four rings (two in a<br>
cofactor, two in the inhibitor being annihilated). Merging the topologies<br>
didn't work because I can't selectively annihilate the inhibitor unless the<br>
cofactor is also annihilated, and use of explicit B-state dummy atom types for<br>
the inhibitor requires manual editing of hundreds of bonded interactions, which<br>
I don't think is effective.<br>
<br>
It seems that there is a patch in Gerrit that has languished for several months<br>
(<a href="https://gerrit.gromacs.org/#/c/2566/" rel="noreferrer" target="_blank">https://gerrit.gromacs.org/#/c/2566/</a>) that appears it might do what I need.<br>
<br>
I'm happy to provide feedback/testing on that patch if someone (Berk?) can tell<br>
me if I can use the intermolecular bondeds to set up a dihedral restraint that<br>
is lambda-dependent (i.e. perturbed as a function of restraint-lambdas in the<br>
.mdp)? The pull code works fine to preserve a few translational restraints that<br>
I need, but the relative orientation is the issue I have. Simply applying an<br>
intermolecular dihedral potential would likely also suffice in lieu of a<br>
restraint if the latter is not possible.<br>
<br>
Getting this feature implemented would be a great benefit and I'm happy to be<br>
the guinea pig for it to get it merged.<br>
<br>
Thanks for any insight!<br>
<br>
-Justin<br>
<br>
--<br>
==================================================<br>
<br>
Justin A. Lemkul, Ph.D.<br>
Ruth L. Kirschstein NRSA Postdoctoral Fellow<br>
<br>
Department of Pharmaceutical Sciences<br>
School of Pharmacy<br>
Health Sciences Facility II, Room 629<br>
University of Maryland, Baltimore<br>
20 Penn St.<br>
Baltimore, MD 21201<br>
<br>
<a href="mailto:jalemkul@outerbanks.umaryland.edu" target="_blank">jalemkul@outerbanks.umaryland.edu</a> | (410) 706-7441<br>
<a href="http://mackerell.umaryland.edu/~jalemkul" rel="noreferrer" target="_blank">http://mackerell.umaryland.edu/~jalemkul</a><br>
<br>
==================================================<br>
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