Re: Ligand atoms moving too fast with FEP

From: Francesco Pietra (chiendarret_at_gmail.com)
Date: Thu Feb 15 2018 - 09:47:51 CST

Hi Brian:

I generally don't recommend NpT simulations for FEP
>

I was following the tutorial, which in other quite similar cases worked
well under NPT. At any event, as there is no membrane, which other type of
simulation?

I commonly make the mistake of not correctly flagging atoms in the PDB
>

I am prone to follow your experience with FEP, and I could easily mismatch
those flags. But should that be corrected later?

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.
>

I am at frwd-01.namd and filename.fep flags are -1.00

Thanks for answering and beg pardon for what I might have misunderstood
from your mail.

francesco

PS I had just submitted to the cluster a NPT MD with the FEP system and
with ts=0.1fs to see what happens. Sometimes files run on inexpensive GPUs
are not well transferable.

On Thu, Feb 15, 2018 at 3:27 PM, Brian Radak <brian.radak_at_gmail.com> wrote:

> 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.
>
> HTH,
> BKR
>
>
> On Thu, Feb 15, 2018 at 3:00 AM, Francesco Pietra <chiendarret_at_gmail.com>
> wrote:
>
>> 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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