On followup: I also ran a GB calculation and the delta G total seems more reasonable -> https://gist.github.com/anonymous/7f039c17c85d82cb880f
________________________________________
From: de Waal, Parker [Parker.DeWaal.vai.org]
Sent: Friday, February 28, 2014 12:11 AM
To: amber.ambermd.org
Subject: [AMBER] MMPBSA.py positive delta G?
Hi Everyone,
I'm trying to determine relative binding energies of the same ligand across various polymorphisms and have run into a potential issue with my MMPBSA calculations. After running a quick test analysis on the wild type receptor the resulting binding energy, delta G, is positive. As I am using the wild type receptor and a known antagonist I don't believe this result makes sense in the context of my system (docking with Vina gave ~-10 kcal mol which I know this is wildly inaccurate and does not compare to the experimental negative delta G). Please find the resulting energy output file here: https://gist.github.com/anonymous/ee99fff75a139f28ccfb
Upon visual inspection and principal component analysis of the ligand it remains very stable in one binding mode within the pocket which further makes me question the positive delta G. Additionally I've checked through my .prmtop files for errors as well as the receptor and ligand masks chosen by MMPBSA.py everything seems to check out just fine.
I've uploaded all of my .prmtop files (solvated, complex, receptor, ligand) an a 100 frame trajector file (taken from ~40 ns into a production run) here
http://research.parkerdewaal.com/vai/mmpbsa.tar.gz . If anyone could verify my calculation or provide insight into receptor-ligand MMBPSA calculations I would greatly appreciate it.
Best,
Parker
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Received on Thu Feb 27 2014 - 22:00:02 PST
