There are 500 valence parameters in SMIRNOFF99Frosst, and we aimed to optimize as many of these as possible. The quantum chemical data sets that we constructed 2.1.2 were successful at covering 481 of these parameters. The remaining 19 (Supporting Table ), which were not modified due to the absence of training data (both in eMolecules, which we drew our coverage set from, and in our other available training data), either describe chemistries that are exceedingly rare in drug-like compounds or were superseded by other higher-priority parameters that matched the same chemical patterns.