Force Fields and Simulation Engines: Lessons Learned from Porting Amber ff14SB and ff19SB to GROMACS

Abstract

The GROMACS molecular dynamics simulation package has historically supported a number of molecular mechanics force fields, including Amber. Force fields have evolved over time and continue to do so through refinement of existing interactions and the definition of additional ones to more faithfully match real-world experiments and higher-level quantum chemistry calculations. Although users have provided a number of conversions of newer Amber force fields over the years, the two most recent Amber protein force fields, ff14SB and ff19SB, had not previously been officially ported to GROMACS. A technical challenge is that ff19SB introduces residue-specific backbone dihedral energy correction maps (CMAPs), which required new support in GROMACS for residue-aware force-field preprocessing and topology generation. Unlike older force fields such as CHARMM27, in which CMAPs are parameterized using only atom types, ff19SB extends this scheme with additional amino-acid typing. Here, we describe how we ported and validated the Amber ff14SB and ff19SB force fields for use with GROMACS as AMBER14SB and AMBER19SB, respectively. The ported force fields reproduce the Amber reference topologies exactly, with per-interaction energies matching to within the single-precision floating-point limit (<10–7 kJ/mol). To achieve this level of consistency between Amber and GROMACS, we resolved discrepancies in their handling of fundamental constants, parameter precision, and improper-dihedral atom ordering logic. In long unrestrained ubiquitin simulations, the converted ff19SB reproduces the conformational free-energy profile obtained with the native Amber implementation. This work provides the first official port of an Amber force field to GROMACS in more than a decade, improving feature parity between the two simulation packages. We provide a reproducible porting and validation procedure that can be used for modified variants and future versions of Amber force fields.