[AMBER] MM/PBSA calculations

From: mish <smncbr.gmail.com>
Date: Fri, 20 Apr 2012 14:06:28 +0200

Dear All,

I have a couple of question related to changing internal dielectric
calculations in MM/PBSA calculations. In Tingjun hou et al JCIM 51,1,69-82
(2010) authors writes that they investigate suitable solute dielectric
constant to cal calculate polar solvation free energies. But if I look at
the values I get a feeling that they used higher dielectric constant also
to calculate electrostatic contribution to the gas phage energies.
Therefore, in reality it was energy is not the gas phage energy but energy
in some organic solvant with diel 2, 3, ..4. I would like to know whether
it is not something which is beyond the definition of MM/PBSA method.
Changing Internal dielectric constant for PB part seems to justified well
in the paper. Can you please comment on this ?

Another question is related with a statement in MM/PBSA tutorial that is
"sum of the electrostatic solvation free energy and MM electrostatic energy
tend to approximately cancel each other out ( so PBELE/GBELE close to Zero)
which should be much smaller than the contributions to it".
I am facing an issue and I think this is somehow related to this fact. I
did MM/PBSA calculations for couple of ligands (of different size) with a
same receptor and what I observe is for small ligands, higher internal
dielectric constant (about 3 or 4 for both Emm and Esol) provides dG in
good agreement to the experiment. So the binding energy increases from -33
(for diel=1) to -20 (diel=3). Whereas for large ligands, increasing
internal dielectric constants for decreases binding energy (-34 (intdl=1)
to -36 (intdl=4)). So for large ligands internal dielectric constant =1 is
the one closer to experimental value. The origin of such difference can
arises from PBELE values form both cases. Changing internal dielectric
constant from 1 to 2, 3,4 .. changes PBELE of small ligands from -8.0 to
-2, whereas for larger ligands it varies from 1.5 to -0.1. I really do
not understand what is the origin of two different behavior in binding
energy for same binding site. In case of large ligands some part of the
ligand interacts better in water whereas small ligands are inside the
cavity and do not interact with water.

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Received on Fri Apr 20 2012 - 05:30:04 PDT
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