For MiniDrugBank we were only partially successful; we were not able to find a 100% partial score for the HX, N2, C*, and HP atom types with SMARTY. It is worth briefly examining these types to understand why. HX was created to address a very specific problem occurring with hydroxyl hydrogens; to match it, a SMIRKS pattern would need to describe an atom in the gamma position (3 bonds away from the primary), but SMARTY sampling extends out only to the beta position. N2 requires multiple SMARTS patterns to be able to match 100% (it combines several different chemical groups into a single atom type) and the bipartite graph matching only allows one working atom type per reference atom type, meaning that SMARTY will never discover it. C* is very similar to other five-membered ring carbon atom types (CW, CC, and CR) in our tests; it also occurs less frequently which would require SMARTY to generate and keep highly specialized SMARTS patterns that match the other atom types uniquely before it could be discovered. In order to find HP, the SMARTS pattern would need a decorator in the beta position, but SMARTY does not currently add decorators to the beta position making it impossible to match this particular atom type. More details about all of these atom types and why they never get a partial score of 100% can be found in the Supporting Information. Nevertheless, SMARTY was fairly successful finding a 100% partial score for most reference atom types in parm99/parm@Frosst with only a few exceptions. In our tests, we were able to find patterns matching 33 out of 37 parm99/parm@Frosst atom types with a 100% partial score -overall an 89.2% success rate. While some reference atom types are not found, this seems to be less a commentary on our chosen sampling algorithm and move set; but a byproduct of the complex human decisions made in constructing parm99/parm@Frosst. The very complex atom typing employed in parm99/parm@Frosst may provide a further argument in favor of moving toward a force field with direct chemical perception and away from those with human defined atom types.