[gmx-users] Crashes during protein-ligand simulation

[Justin A. Lemkul]

On 7/6/12 1:12 AM, James Starlight wrote:
> Dear Gromacs users!
>
> I have some problems with the simulation of protein-ligand complex
> embedded in the ccl4-water environment. In addition there are some
> crystallography waters (xw) embedded in the protein interiour of the
> protein. I've done equilibration and minimisation of my system and run
> it in NVT ensemble.
>
> Finally I've already simulated this system in the apo form as well as
> without XW and there were no any problems.
>
> In the current case my system always crashed after 10-15 ns of
> simulation with the errors like
>
> Step 6651310, time 13302.6 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> rms 0.060675, max 1.520945 (between atoms 3132 and 3130)
> bonds that rotated more than 30 degrees:
>   atom 1 atom 2  angle  previous, current, constraint length
>     3148   3147   90.0    0.1281   0.1483      0.1000
>     3150   3149   90.0    0.1084   0.1444      0.1000
>     3131   3130   90.0    0.1321   0.1325      0.1000
>     3132   3130   90.0    0.1067   0.2521      0.1000
>
> -------------------------------------------------------
> Program mdrun_mpi.openmpi, VERSION 4.5.5
> Source code file: /tmp/build/gromacs-4.5.5/src/mdlib/constr.c, line: 189
>
>
> here both atoms 3132 and 3130 are from LIGAND.
>
> During data analysing I didnt observed any serious artifacts in that
> system. In addition RMSD both of protein and ligand were very stable.
> Finally there are no fluctuations in energy or temperature. So I could
> understand why this crasshes could occur. If I try to continue this
> simulation from the crasshed checkpoint my simulation always goon but
> within next 5-10ns I've always obtain second crash etc.
>
> This is the last step from log file
>
> DD  step 6649999  vol min/aver 0.758  load imb.: force  1.0%  pme
> mesh/force 0.708
>
>             Step           Time         Lambda
>          6650000    13300.00000        0.00000
>
>     Energies (kJ/mol)
>            Angle       G96Angle    Proper Dih.  Improper Dih.          LJ-14
>      5.78299e+01    1.24988e+04    2.10966e+03    1.81619e+03    8.94229e+01
>       Coulomb-14        LJ (SR)        LJ (LR)  Disper. corr.   Coulomb (SR)
>      4.65481e+04    8.27301e+04   -6.89535e+03   -2.15286e+03   -7.16722e+05
>     Coul. recip.      Potential    Kinetic En.   Total Energy  Conserved En.
>     -1.72813e+05   -7.52733e+05    1.46708e+05   -6.06025e+05   -1.37045e+06
>      Temperature Pres. DC (bar) Pressure (bar)   Constr. rmsd
>      3.10968e+02   -9.74796e+01    2.52993e+02    1.55693e-05
>
>
> Could you explain me what could be wrong with that system and what
> addition data should I provide to help sheld light on that problem ?
>

If the addition of a ligand causes the simulation to crash (and the simulation 
runs normally in the apo form with and without crystal waters), then that sounds 
like a problem with the ligand topology or its initial placement.

What is the ligand?  How did you generate and validate its topology?  How did 
you place it?

-Justin

-- 
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Justin A. Lemkul, Ph.D.
Research Scientist
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

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