Non-bonded pair interactions error for gromacs-2024.5 but not present in 2018

GROMACS version: 2024.5

Dear Gromacs users,

I am attempting to run a solvation free energy calculation of an organic molecule: merocyanine (the molecule contains 42 atoms). I solvated the system in a cubic box (4x4x4) including 1362 tip3p water molecules. I am decoupling the vdw and coulomb terms for alchemical simulations. The distance between the two farthest atom is approximately 1.2 nm.

When I am running the mdrun with gromacs-2024, I am getting the error: “4-non-bonded pair interactions beyond the pair-list cutoff”, but I am not getting that error when I am using gromacs-2018.6. I am using coupl-intramol = no in the mdp file and I changed that to “yes” and now in gromacs-2024 simulations are running.

Is it okay to use coupl-intramol = yes for solvation free energy calculations of a molecule containing 42 atoms? Also does this “non-bonded pair interaction” error have to do anything with gromacs versions as it seems that 2018.6 is working fine but not 2024.5? Any help or suggestions will be highly appreciated, thank you.

2018 didn’t have this check, but the issue is also present there. So one can potentially get incorrect results with 2018.

Thank you for your reply, I have been running the calculations with gromacs-2018.6. However, should we use couple-intramol = yes when we get this error. The solute molecule is an organic molecule with 42 atoms, where the end-to-end distance is approximately 1.3 nm. Using couple-intramol = yes is working fine. What do you suggest? Any suggestions is highly appreciated, thank you.

If you have sufficiently frequent energy output, you can check if you see spikes in the total energy, or maybe easier in the conserved energy quantity.