FFLUX : towards a force field based on interacting quantum atoms and kriging

Force fields have been an integral part of computational chemistry for decades, providing invaluable insight and facilitating the better understanding of biomolecular system behaviour. Despite the many benefits of a force field, there continue to be deficiencies as a result of the classical architecture they are based upon. Some deficiencies, such as a point charge electrostatic description instead of a multipole moment description, have been addressed over time, permitted by the ever-increasing computational power available. However, whilst incorporating such significant improvements has improved force field accuracy, many still fail to describe several chemical effects including polarisation, non-covalent interactions and secondary/tertiary structural effects. Furthermore, force fields often fail to provide consistency when compared with other force fields. In other words, no force field is reliably performing more accurately than others, when applied to a variety of related problems. The work presented herein develops a next-generation force field entitled FFLUX, which features a novel architecture very different to any other force field. FFLUX is designed to capture the relationship between geometry and energy through a machine learning method known as kriging. Instead of a series of parameterised potentials, FFLUX uses a collection of atomic energy kriging models to make energy predictions. The energies describing atoms within FFLUX are obtained from the Interacting Quantum Atoms (IQA) energy partitioning approach, which in turn derives the energies from the electron density and nuclear charges of topological atoms described by Quantum Chemical Topology (QCT). IQA energies are shown to provide a unique insight into the relationship between geometry and energy, allowing the identification of explicit atoms and energies contributing towards torsional barriers within various systems. The IQA energies can be modelled to within 2.6% accuracy, as shown for a series of small systems including weakly bound complexes. The energies also allow an interpretation of how an atom feels its surrounding environment through intra-atomic, covalent and electrostatic energetic descriptions, which typically are seen to converge within a ~7 - 8 A horizon radius around an atom or small system. These energy convergence results are particularly relevant to tackling the transferability theme within force field development. Where energies are seen to converge, a proximity limit on the geometrical description needed for a transferable energy model is defined. Finally, the FFLUX force field is validated through successfully optimising distorted geometries of a series of small molecules, to near-ab initio accuracy.