Molecular mechanics (MM) force fields are empirical models of molecular potential energy surfaces, which yield the potential energy and atomic forces as a function of the atomic positions. Force fields are a crucial component of molecular simulations in many domains of chemistry and biophysics. In particular, force fields are used in simulations of biomolecular systems that may include biopolymers, aqueous solvent, and small molecules such as metabolites and therapeutics. They are also fundamental to technologies used in computer-aided drug design, such as molecular docking and simulation-based calculations of proteinligand binding free energies. Decades of work have led to relatively refined force fields for proteins made up of the 20 common amino acids. However, it is more difficult to develop a high quality general force field, i.e., one that applies to the wide range of small, organic molecules of interest in biology and drug discovery, due to the high diversity of the chemical space that must be considered. For example, the nearly 100 million compounds in the PubChem database embody many different combinations of varied functional groups and heterocycles.