Re: [AMBER] Positive delta G in MM-PBSA

From: Jason Swails <>
Date: Sat, 14 Nov 2015 13:14:41 -0500

On Sat, Nov 14, 2015 at 12:53 PM, Hira Jabeen <>

> Dear Jason,
> I used 20ns complex for the calculation of MM-PBSA. The RMSD of the
> complex is stable with average value of 2.76 Å and reaches the maximum
> value of 3.56 Å. The results are quite disappointing, i am getting high
> positive values of delta G while calculating MMPBSA in AMBER12 and AMBER14.
> It might be due to high positive values of Van Der Waals, plz help me out
> in resolving this problem. The input file is attached here.

​This is the output file (although the input file information is stored in

There is nothing that stands out as a very obvious problem looking at this
output file. The 1-4 nonbonded interactions seem to cancel, which
indicates no L-J or charge parameter differences between your bound and
unbound states. The individual energies themselves are well within the
expected ranges for "typical" systems.

I think this result is "real" given your original MD simulation. In
particular, a high, positive vdW contribution in the bound state would
suggest to me that the ligand is packed too tightly, and a little bit
unfavorably, inside the binding pocket. The only contribution to the DELTA
vdW energies are the ligand <-> receptor vdW interactions (since it is a
pairwise decomposable potential). As a result, it's clear that the vdW
interactions between ligand and receptor in the bound complex are very
unfavorable, and there is significant Lennard-Jones repulsion happening
there (without a corresponding favorable charge-charge interaction to

​I wonder how the ligand stayed bound in your simulation at all. Or did
you hold it in there with restraints?


Jason M. Swails
Rutgers University
Postdoctoral Researcher
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Received on Sat Nov 14 2015 - 10:30:03 PST
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