A FFLUX Water Model: Flexible, Polarizable and with a Multipolar Description of Electrostatics

Key to progress in molecular simulation is the development of advanced models that go beyond the limitations of traditional force fields that employ a fixed, point charge‐based description of electrostatics. Taking water as an example system, the FFLUX framework is shown capable of producing models that are flexible, polarizable and have a multipolar description of the electrostatics. The kriging machine‐learning methods used in FFLUX are able to reproduce the intramolecular potential energy surface and multipole moments of a single water molecule with chemical accuracy using as few as 50 training configurations. Molecular dynamics simulations of water clusters (25–216 molecules) using the new FFLUX model reveal that incorporating charge‐quadrupole, dipole–dipole, and quadrupole–charge interactions into the description of the electrostatics results in significant changes to the intermolecular structuring of the water molecules. © 2019 The Authors. Journal of Computational Chemistry published by Wiley Periodicals, Inc. Traditional molecular force fields are inevitably limited in their accuracy and transferability. FFLUX is a new approach to force field development that aims to leverage quantum chemical topology (QCT) and machine learning to provide a quantum mechanical description the potential energy surface of systems into a force field. Here, a variety of FFLUX force fields have been created for water and their performance analyzed both at the single molecule level and for the simulation of water clusters.