[AMBER] strategies to speed up MM/GBSA screening

From: Thomas Evangelidis <tevang3.gmail.com>
Date: Wed, 13 Jul 2016 13:08:31 +0200


I want to screen through MM/GBSA a few thousand small molecules that are
superimposed on the crystal ligand in the binding pocket of a protein. The
idea is not to calculate absolute binding free energies, but to improve the
ranking by discarding those that don't fit well into the cavity​. For this
purpose I impose restraints to the protein atoms and leave flexible only
the side-chains that are close to the crystal ligand. However, this incurs
a computational slow down. Since I am not really interested in the dynamics
of the protein atoms that are not in the binding cavity, is there any way
to prevent sander from calculating positions and velocities for these
atoms? I read in the manual that "ibelly" is not compatible with implicit
solvent and moreover it does not provide any significant speed gains. The
other option would be to reduce the protein to the binding cavity and
simulate only that. However, I am not sure if this may lead to significant
loss of accuracy in some cases.

I would like to know the opinion of people that are more experienced than
me in MM/GBSA screening. Below is my input script.

# production MD

   nstlim=500, cut=12.0, igb=8, saltcon=0.2,
   ntpr=100, ntwr=100000, ntt=3, gamma_ln=0.0,
   ntx=1, irest=0,
   ntc=2, ntf=2, tol=0.000001,
   dt=0.002, ntb=0, ig=71277,
   ioutfm=1, ntxo=2, ntwx=100,
   ntr=1, ntrx=1, restraint_wt=50,
   restraintmask="! ( (:LIG <:5) &! (@CA,C,O,N,H) )"


Thomas Evangelidis
Research Specialist
CEITEC - Central European Institute of Technology
Masaryk University
Kamenice 5/A35/1S081,
62500 Brno, Czech Republic
email: tevang.pharm.uoa.gr
website: https://sites.google.com/site/thomasevangelidishomepage/
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Received on Wed Jul 13 2016 - 04:30:03 PDT
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