FEP on an amino acid ligand

From: Thomas Albers (talbers_at_binghamton.edu)
Date: Mon Jan 21 2013 - 19:44:20 CST


We would like to run FEP on some amino acids in the binding pocket of
our amino acid transporter to get an idea of what accounts for the
observed binding affinities but when I'm running the FEP calculation
the simulation blows up within a few hundred timesteps. At constant
pressure, NAMD complains about the periodic cell having become to
small, and at constant volume one sees atoms moving too fast.

So far, I have built a topology of the amino acid ligand with the help
of the hybrid topologies (top_all27_hybrid.inp). I also have a model
of the transporter with its ligand in the binding pocket. With the
coordinates of the ligand and the internal coordinates in the topology
file I can build a .psf and .pdb file for the new ligand, and I have
also built a new model, consisting of the transporter with the FEP

The ligand is glycine, which is transformed into alanine by turning
the CH2 group into a CH(CH3) group. These are the alchemical
alch on
alchType fep
alchEquilSteps 5000
alchFile ALA.fep
alchCol B
alchOutFreq 10
alchOutFile ALA.fepout
alchDecouple off
alchVdwLambdaEnd 1.0
alchElecLambdaStart 0.5
alchVdWShiftCoeff 6.0
alchLambda 0
alchLambda2 .05
run 10000

However, when running a normal simulation with the new coordinates
(the glycine ligand without the exnihilated atoms), this simulation
runs just fine.

Something is wrong here, and I cannot see what it is.


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