In our workflow, for any molecule in the test, it can only be assigned as "yes" or "no" for the hit, and "yes" or "no' for a cluster ID. a, b, c, d are the structure counts in the contingency table for hit vs.(versus) not-hit and in-this-cluster vs. not-in-this-cluster, and n is the total number of the structures. After the test, any cluster showing p-value less than or equal to 0.05 is considered as a hit enriched SAR cluster. This virtual SAR enrichment analysis allows us to identify which chemical groups and structures are most likely to be the true binders for the pocket with dynamic SAR range suitable for medicinal chemists to further optimize. We then selected the top N GBVI/WSA ΔG score molecule(s) from each hit SAR cluster as a hit SAR scaffold(s). By selecting the best compound(s) from each hit cluster, we were able to focus on the most promising binders for the next step processing for the de novo synthesis, or the archived and virtual libraries searching, as well as the protein ligand interaction site profiling.