Construction of a Gaussian Process Regression Model of Formamide for Use in Molecular Simulations

FFLUX, a novel force field based on quantum chemical topology, can perform molecular dynamics simulations with flexible multipole moments that change with geometry. This is enabled by Gaussian process regression machine learning models, which accurately predict atomic energies and multipole moments up to the hexadecapole. We have constructed a model of the formamide monomer at the B3LYP/aug-cc-pVTZ level of theory capable of sub-kJ mol^–1 accuracy, with the maximum prediction error for the molecule being 0.8 kJ mol^–1. This model was used in FFLUX simulations along with Lennard-Jones parameters to successfully optimize the geometry of formamide dimers with errors smaller than 0.1 Å compared to those obtained with D3-corrected B3LYP/aug-cc-pVTZ. Comparisons were also made to a force field constructed with static multipole moments and Lennard-Jones parameters. FFLUX recovers the expected energy ranking of dimers compared to the literature, and changes in CO and C–N bond lengths associated with hydrogen bonding were found to be consistent with density functional theory.