Critical isofrom selectivity in molecular dynamics

From: M RCC (mkr3j2c1_at_gmail.com)
Date: Mon Sep 24 2018 - 06:23:14 CDT

 Dear NAMD Users,

I have used Amber and Gromacs to a little extent, but novice with NAMD

I need your suggestion for an issue regarding isoform selectivity of
inhibitors.
my protein of interest has two isoforms, (Let us say, IsoformA and
IsoformB). Both have more than 80% of sequence identity. In this case, few
inhibitors are more selective towards IsoformA, and few are towards B.
Crystal structure of these compounds with both Isoforms are identical.
Even the authors reported that there is no difference in the between
binding mode of inhibitors in the crystal structures.

Active site residues of both isoforms are identical. residue difference was
found only beyond 10A of the active site.

How I can provide data through computation/Molecular dynamics, for the
compound which I designed is selective towards one Isoform?

What kind of calculations I should perform?

I did MD for 100ns and calculated binding energy (MMPBSA.py), I could not
find any difference in the energy, -means they are not comparable with
their activity.

Thanks in advance.

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