As in the naïve RL-AL experiment, we use 𝑁 batch of 256 and 𝑁 acquired of 128 in one loop with UCB acquisition (Methods) as a baseline case. We use the ROCS oracle for experimentation due to its better computational efficiency compared to docking . A summary of all configuration parameters is provided in the Supporting Information (Supporting Table ). We test the efficiency of each configuration from the perspective of number of unique hit scaffolds, predicted affinity/overlay score greater than the native ligand, generated and acquired per oracle call over 30 000 oracle calls and the diversity of the resulting generated hit scaffolds (Figure ).