[gmx-users] Umbrella sampling error with drug molecule

[Khuong Truong Gia]

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?
If so, how can I pull a flexible molecule? Please give me some suggestion.
Thanks in advance.

Best regards,
Khuong