[gmx-users] Dihedral parameters from QM and MM relaxed surface scans

[Eric Smoll]

Hello Gromacs Users,

I am trying to reproduce some published forcefield development work. In
this paper, dihedral parameters are derived from QM and MM relaxed surface
scan data collected on individual small molecules in vacuum.

My replication workflow is as follows. The MM relaxed surface scan
trajectory was prepared by concatenating the final frame of a set of energy
minimization calculations. Each energy minimization held the dihedral of
interest at a desired angle with a 1000 kJ/mol dihedral restraint. Other
DOF's were allowed to relax with the "steep" algorithm in single-precision
GROMACS 2018.1 to machine precision. A "restrained" dihedral PES was
calculated by collecting the molecule's potential as a function of dihedral
angle *with the restraint on the dihedral of interest*.

An "unrestrained" dihedral PES was also calculated by removing the dihedral
restraint on the dihedral of interest and calculating the energy with the
rerun feature of mdrun.

I find that the "restrained" MM dihedral PES is in excellent quantitative
agreement with QM relaxed surface scan data. The "unrestrained" MM dihedral
PES is only in qualitative agreement with the QM results. Peaks and dips in
the "unrestrained" PES are exaggerated when compared to the "restrained"
PES.

As far as I understand, the "unrestrained" PES should be more
appropriate/accurate than the "restrained" PES. Am I correct? Is there a
flaw in my workflow?

Best,
Eric