where N = total number of evaluations for the baseline; N s = total number of evaluations for a given explorer; n = number of compounds from baseline exceeding a score threshold, where score can be classification, pKi, or their rank order; n s = number of compounds from explorer exceeding the score threshold. Compound selection. For the single concentration assay we selected 400 compounds for each method. We removed pan-assay interference (PAINS) compounds, compounds containing unwanted functional groups, for example reactive moieties, compounds that contained 3 or more stereocenters, and HE compounds for which MEL caps were not replaced from the entire list of compounds returned by each method. We then clustered the compounds applying a diversity cutoff of 0.4 Tanimoto similarity using 1024-bit ECFP4 fingerprints and computationally selected, without human intervention, up to the three top-scoring compounds per similarity cluster in a round-robin fashion. We verified that both sets contained 400 distinct compounds by de-duplication. There were no inter-explorer overlaps. The maximum compound similarity across all 800 compounds was 0.93 from compounds belonging to the same high-scoring cluster. Enamine rank-ordered both lists of 400 compounds for synthesizability and prioritized synthesis accordingly. We purchased the first 125 that completed synthesis, resulting in 123 compounds identified with the NGT method, and 129 with the HE method for a total of 252.