On Wed, 2014-08-20 at 11:11 -0700, zahra khatti wrote:
> Dear Amber users
>
> I obtained positive free energy from mmpbsa.py.
MM/PBSA absolute binding free energies are frequently unreliable. It is
useful mainly for rank-ordering binding affinities for related systems.
> In my case the receptor and ligand didn't joint together. The distance between them
> is about 1-2 angstrom. Is this related to positive free energy?
Let's have a look:
[snip]
> Differences (Complex - Receptor - Ligand):
> Energy Component Average Std. Dev. Std. Err. of Mean
> -------------------------------------------------------------------------------
> VDWAALS -50.0785 1.0295 0.0084
> EEL -1.1552 0.3301 0.0027
> EPB 7.3643 0.8011 0.0065
> ENPOLAR -22.2317 0.3450 0.0028
> EDISPER 354.9084 4.6963 0.0383
Yikes. The EDISPER component of your binding free energy is +350
kcal/mole. Combining that with the repulsive ENPOLAR term, that means
your _total_ non-polar solvation free energy contribution to binding is
about +330 kcal/mole, which seems outrageous to me.
It seems to me that this is a fairly frequent occurrence with the
"inp=2" non-polar solvation free energy model, so I can't say I
recommend using it. I suggest adding inp=1 to the &pb section of your
input file to use the more prototypical, simple SASA-based nonpolar
solvation approximation.
.Developers: Perhaps we should consider either turning the default back
to inp=1 or removing the default choice altogether and requiring users
to specify it? inp=2 seems to be causing a lot more problems than it
solves and gives ludicrous answers more often than inp=1.
All the best,
Jason
--
Jason M. Swails
BioMaPS,
Rutgers University
Postdoctoral Researcher
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Received on Wed Aug 20 2014 - 12:00:02 PDT
