NPT and position restraints

GROMACS version: 2021.2
GROMACS modification: No

I am running a MARTINI CG simulation using MARTINI V2. The system comprises of a macromolecule with over 6000 CG beads and a solute with 150+ beads, both in 500K water beads. When I apply position restraints on all beads of the macromolecule and run NPT using Berendsen barostat the water does not return to the cubic box shape even after 1,000,000 steps of 0.1 ps. On the other hand, if position restraints are not applied, the cubic box shape is obtained after about 100,000 steps or even less.

After Berendsen, I switch to Parrinello-Rahman barostat for further NPT equilibration and production runs but the same aberrant behaviour of water box continues. In many cases, the simulation crashed at the first step of production run.

Please let me know what could be the possible reason behind this and the workaround. I donot want to remove the position restraints since these maintain the macromolecule in the correct shape.

Thanks in advance for your help.


It could be that ref-coord-scaling = com will fix your issue.

Dear Hess,

refcoord-scalling =com was already there in the MDP. Without that, grompp issues a warning with position restraints.


Then I don’t know what could be the issue.

But I don’t understand what your setup is and what you observe. You use the word “return”. That would imply the water is originally in a cubic box, then somehow goes out of the cubic box and then comes back? In a periodic system all molecules are always “in the box”.