The Impact of Using Single Atomistic Long-Range Cutoff Schemes with the GROMOS 54A7 Force Field.

Abstract

With the recent increase in computing power, the molecular modeling community is now more focused on improving the accuracy and overall quality of biomolecular simulations. For the available simulation packages, force fields, and all other associated methods used, this relates to how well they describe the conformational space and thermodynamic properties of a biomolecular system. The parameter sets of GROMOS force fields have been parametrized and validated with the reaction field (RF) method using charge groups and a twin-range cutoff scheme (0.8/1.4 nm). However, the most recent versions of GROMACS (since v.2016) discontinued the support for charge groups. To take full advantage of the newer and faster versions of this software package with GROMOS 54A7 and RF, we need to evaluate the impact of using a single cutoff scheme (vs twin-range) and of using the Verlet list update method (which is atomistic) compared to the group-based cutoff scheme. Our results show that the GROMOS 54A7 force field seems consistent with a single cutoff, since the resulting conformation and protonation ensembles were indistinguishable. The GROMOS parametrization procedure was also reproduced using an atomistic cutoff scheme, and we have observed that the hydration free energy values of small amino acid side-chain analogues were similar to the ones obtained with the group-based protocol. We do observe a small impact of the atomistic cutoff scheme in the conformational space of the model systems studied (G1-PAMAM and DMPC). However, since the structural properties of these systems are well converged for the cutoff range used (1.4-2.0 nm), unlike with the group-based cutoff schemes, we are confident that the atomistic cutoff can be adopted with RF for MD and constant-pH MD biomolecular simulations using the GROMOS 54A7 force field.