New Angles on Standard Force Fields: Toward a General Approach for Treating Atomic-Level Anisotropy

Nearly all standard force fields
employ the “sum-of-spheres”
approximation, which models intermolecular interactions purely in
terms of interatomic distances. Nonetheless, atoms in molecules can
have significantly nonspherical shapes, leading to interatomic interaction
energies with strong orientation dependencies. Neglecting this “atomic-level
anisotropy” can lead to significant errors in predicting interaction
energies. Herein, we propose a simple, transferable, and computationally
efficient model (MASTIFF) whereby atomic-level orientation dependence
can be incorporated into ab initio intermolecular force fields. MASTIFF
includes anisotropic exchange-repulsion, charge penetration, and dispersion
effects, in conjunction with a standard treatment of anisotropic long-range
(multipolar) electrostatics. To validate our approach, we benchmark
MASTIFF against various sum-of-spheres models over a large library
of intermolecular interactions between small organic molecules. MASTIFF
achieves quantitative accuracy, with respect to both high-level electronic
structure theory and experiment, thus showing promise as a basis for
“next-generation” force field development.