Figure 3.

In the LIT-PCBA analysis, early enrichment was observed for OPRK1—for all Tanimoto coefficients $t>\sim$0.2, the fraction of actives with Tanimoto score $>t$ is much larger than the fraction of decoys with that score (see Figure 2). This suggests that fingerprints produce useful early enrichment of active molecules, at least for this one protein target. We sought to understand if the high-scoring actives represented novel drug candidates that could not be easily identified by simple modifications to the active drug used as a fingerprint query. There are only 24 actives in the OPRK1 data set, and only 5 of these showed Tanimoto score $>0.5$ to the initial query; we manually inspected the structures of these compounds. All 5 are built on the same scaffold as the query (in red), and are obvious variations that should be identified through standard enumeration (i.e., no new scaffold are explored). Similar plots are provided for GBA and PPARG in Supplementary Figures S6 and S7.