[gmx-users] Umbrella sampling error with drug molecule

[Justin Lemkul]

On 3/1/16 7:59 PM, Khuong Truong Gia wrote:
> Hi all,
>
>
> I am using gromacs to run umbrella sampling simulation with a drug molecule
> (polymer). I got force field from PRODRG.
> When run pulling the drug I got this error:
>
> step 86530014: Water molecule starting at atom 8336 can not be settled.
> Check for bad contacts and/or reduce the timestep if appropriate.
> Wrote pdb files with previous and current coordinates
>
> WARNING: Listed nonbonded interaction between particles 49 and 59
> at distance 3.355 which is larger than the table limit 2.076 nm.
>
> This is likely either a 1,4 interaction, or a listed interaction inside
> a smaller molecule you are decoupling during a free energy calculation.
> Since interactions at distances beyond the table cannot be computed,
> they are skipped until they are inside the table limit again. You will
> only see this message once, even if it occurs for several interactions.
>
> IMPORTANT: This should not happen in a stable simulation, so there is
> probably something wrong with your system. Only change the table-extension
> distance in the mdp file if you are really sure that is the reason.
>
>
>
> Step 86530015, time 173060 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> rms 14.609595, max 619.843628 (between atoms 46 and 47)
> bonds that rotated more than 30 degrees:
>   atom 1 atom 2  angle  previous, current, constraint length
>        4      5   90.0    0.1056   0.1073      0.1000
>       18     19   32.4    0.1495   0.1588      0.1440
>       20     21   50.7    0.1444   0.1265      0.1520
>       20     28   32.7    0.1429   0.1885      0.1440
>       .......
> It's seem that the drug molecule is very flexible and it makes the system
> blowing up. Is it right?

Not likely.  A sound topology should run stably as long as all the other 
settings are sensible.  But PRODRG topologies are of inadequate quality for any 
reliable simulation, so you need to optimize it.

Then follow the normal troubleshooting advice.

http://www.gromacs.org/Documentation/Terminology/Blowing_Up#Diagnosing_an_Unstable_System

-Justin

-- 
==================================================

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

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