Re: Ligand atoms moving too fast with FEP

From: Brian Radak (brian.radak_at_gmail.com)
Date: Fri Feb 16 2018 - 07:47:18 CST

On Thu, Feb 15, 2018 at 10:47 AM, Francesco Pietra <chiendarret_at_gmail.com>
wrote:

> 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?
>

This is certainly just my opinion and not necessarily the prevailing
wisdom. My understanding is that NVT generally has about 5-10% better
performance. It should also give nearly identical results for a well chosen
density.

>
>
> 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?
>

I meant forgetting to flag an atom that should be included in the ligand.
That's just such a silly mistake that I look for it first (and has solved
the issue more times than I care to admit).

>
> 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.
>

I'd be a bit surprised if the equilibrated inputs are just "no good" for
FEP. I guess you could minimize and randomize velociites before doing FEP?
I've personally never had a situation where the solution was to use a
smaller timestep during equilibration.

>
> 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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