Re: Ligand atoms moving too fast with FEP

From: Brian Radak (
Date: Thu Feb 15 2018 - 08:27:42 CST

I generally don't recommend NpT simulations for FEP (unless you have a
membrane) - the virial is goofy for dual-topology simulations, but
doubtfully catastrophically so. That's probably not the issue at all, but
it's something to try.

At the risk of being slightly insulting, I commonly make the mistake of not
correctly flagging atoms in the PDB - maybe check the ALCH summary after
the PSF STRUCTURE SUMMARY? Also a silly error, but worth checking. Also,
make sure that you are flagging the atoms to start at the correct, fully
interacting, endpoint. Assuming you are scanning alchLambda 0 -> 1, the
flag should be -1, not 1.


On Thu, Feb 15, 2018 at 3:00 AM, Francesco Pietra <>

> Hallo:
> While I had no problems so far with protein-ligand FEP, with a new similar
> ligand, parameterized for charmm36 at the same quality level as before for
> the other ligands, FEP crashed.
> The new system had been subjected to charmm36 npt MD for 1,000,000 steps
> at ts=1.0fs on a single node CPU-GPU box, reaching constant rmsd vs frame.
> With frwd FEP, carried out on a nextscale cluster on two Broadwell nodes
> (72 cores) at ts=1.0fs, the simulation crashed nearly immediately (within
> 19s) with three atoms of the ligand moving two fast.
> What about resubmitting classical MD on the cluster for > 1,000,000 steps?
> Or what could be better?
> thanks for advice
> francesco pietra

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