  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 non-spherical
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.
