[gmx-users] Lincs constraints failure

[Qinghua Liao]

Hello,

I have searched on Google for the LINCS warning problems, and there are 
already many discussions,
but I guess that my situation might be different.

I have a system of protein/micelles/water_ions in a dodecahedral water 
box. The system is fully equilibrated by several steps.

1. minimizations (steep, cg) with positional restraints (1000 kJ/mol 
nm2) on protein and micelles,
2. 500 ps NVT equilibration, time step 1 fs, positional restraints (1000 
kJ/mol nm2) on protein and micelles,
3. 500 ps NPT equilibration, time step 1 fs, positional restraints (1000 
kJ/mol nm2) on protein and micelles,
4. 500 ps NPT equilibration, time step 1 fs, positional restraints (800 
kJ/mol nm2) on protein and micelles,
...500 ps, restraints, 600 kJ/mol nm2, 1fs
...500 ps,  restraints, 400 kJ/mol nm2, 1fs
...500 ps restraints, 200 kJ/mol nm2,  1fs
... 500 ps restraints, 100 kJ/mol nm2, 1 fs

5. 15 ns equilibration, positional restraints (100 kJ/mol nm2) only on 
protein, letting the micelles assemble, time step 1 fs
6. 5 ns MD simulation, without any restraints, time step 2 fs

For all these steps, the constraints were applied to h-bonds, which is 
the same for following simulations.
And the I started a Hamiltonian replica exchange simulation, 4 replicas 
were chosen, time step is 2fs.
But the simulation crashed at the simulation time of 25 ns. The error is 
shown like:
#
step 12855987: Water molecule starting at atom 66929 can not be settled.
Check for bad contacts and/or reduce the timestep if appropriate.
Wrote pdb files with previous and current coordinates
Wrote pdb files with previous and current coordinates
#
Step 12855991, time 25712 (ps)  LINCS WARNING in simulation 3
relative constraint deviation after LINCS:
rms 0.000678, max 0.010615 (between atoms 3541 and 3542)
bonds that rotated more than 30 degrees:
  atom 1 atom 2  angle  previous, current, constraint length
    3541   3543   90.0    0.1010   0.1020      0.1010
#

Atom 3541 is ND2 of ASN227, and atom 3543 is HD22 bonded to atom 3541. I 
checked the trajectory file, and I didn't find Asn227 doing something 
improperly.

I also found that the constraints failure happened faster if I used 2 fs 
with constraints for all bonds. I believe that a time step of 1 fs will 
work, which also means
more computing time since the system is very big. Any suggestions? 
Thanks very much!



All the best,
Qinghua