On combining the results from every iteration in all simulations (10,000, 50,000, and 100,000 iterations at all temperatures) we find a 100% partial score for the majority of smirnoff99Frosst reference fragment types (Table ). Heat maps for MiniDrugBank, like the examples shown for torsions in AlkEthOH and PhEthOH (Figure ), are available in the Supporting Information. There are five bond, two angle, 19 torsion, and one nonbonded reference fragment types where SMIRKY never finds a 100% partial score. Potential reasons for missing these fragment types are summarized in this section and discussed in further detail in the Supporting Information. While it would be ideal to find all the fragment types, SMIRKY is able to find SMIRKS patterns that agree with 91% of the smirnoff99Frosst fragment types, indicating that we do recover a great deal of the target chemistry. As with SMARTY, there are a few fragment types that SMIRKY never recovers. In the Supporting Information we provide information about these missing fragment types, exploring in more detail why some are so challenging and why others are undiscoverable with SMIRKY's current algorithm. In the following paragraphs we summarize the categories where SMIRKY's algorithm could be improved in order to discover these missing types.