To estimate the time necessary to screen the entire enumerated 3D ZINC-22 library of 4.8 billion molecules, we extrapolated from the empirical times obtained during the construction of the 100 million scale AmpC and D4 HNSWs. The construction time was recorded cumulatively for each 1 million molecules added to the HNSW on 50 cores of a 2.40GHz Intel Xeon Gold 6240R. The theoretical construction time follows an N log(N) relationship, and we fit our empirical times to this relationship to estimate the time required to build an HNSW comprising 4.8 billion molecules (Supplementary Figure ). We used the slightly slower estimates obtained from the D4 empirical data for this analysis.