Our observation that ABFE calculations outperform docking in virtual compound screening would not be very meaningful if we were comparing it with an unreliable docking method. However, our docking calculations do yield good enrichment metrics for the focused Tier 1 and Tier 2 sets, as assessed by the AUC statistic (Table ). Thus, our docking AUCs range from 0.82 to 0.87, and our 1% enrichment factors range from 26 to 30. Comparing with a prior study (i.e., the original DUD-E paper ), we also observed that our docking calculations over each target's full DUD-E dataset of 18,000-28,000 compounds achieve substantially better enrichment metrics for BACE1 and CDK2, and similar metrics for thrombin (Table ). These favorable results for our baseline docking method indicate that the enhanced differentiation of actives from decoys afforded by ABFE represents a meaningful advance. It also suggests that the docked poses generate by our docking procedure are suitable as starting conformations for downstream ABFE calculations.