Re: Ligand atoms moving too fast with FEP

From: Francesco Pietra (chiendarret_at_gmail.com)
Date: Fri Feb 16 2018 - 09:31:08 CST

I meant NTP MD at ts=0.1fs, not minimization, which does not feel the value
of ts. Actually, however, I checked that NTP with ts=1.0fs does not crash
on the cluster, so that I launched a one-day long NPT on two nodes (72
cpus). After that, I'll also have (hopefully) a better conformation of the
ligand to use as reference structure for FEP (the starting structure of the
ligand is from NMR; it is a compound that we isolated long ago from
corals). Clearly - as yoy supposed - that ligand atom were moving to fast
was due to the conditions for FEP.

I understand now that you meant NVT. I'll try to educate myself about NVT,
about which I have no experience. I want to simulate human-body conditions
as closely as possible. This is why I choose NTP.

thanks
francesco

On Fri, Feb 16, 2018 at 2:47 PM, Brian Radak <brian.radak_at_gmail.com> wrote:

> 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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