Initially, the hit rate of the RL agent is comparable to VS. However, after ~15 000 oracle calls, the RL agent learns to reliably generate hits, after which time the productivity of the generative model grows rapidly, and by 30 000 calls, the RL method has produced more unique hits (79±18) and scaffolds (35±7) for ROCs than contained in the virtual library (Figure ). The final overall oracle call efficiency is 0.12% for ROCs. For docking, 37±8 hits are generated (all unique scaffolds), a lower number than contained in the virtual library, for a docking oracle efficiency of 0.12%. The compounds generated via RL exhibit higher average component scores due to MPO (Supporting Figure ).