Here, we first detail the proteins and ligands used in the study and how they were prepared for calculations. We then describe the computational approach used to compare ABFE calculations with docking in the context of structure-based virtual compound screening. In brief, for each target and its associated active and decoy compounds, we first used docking to rank all of the actives and decoys and identify the top-scoring form (protonation state, stereoisomer, tautomer) of each compound. Then, for two balanced sets of 30 compounds, ten docked poses of the top-scoring form were equilibrated in the binding site by MD, and any poses which moved away from the binding site were discarded. Full ABFE calculations were then run, starting from the best-scored remaining poses. The same ten poses were run twice through the full calculation, comprising MD equilibration and ABFE calculations, using different random number seeds, in order to generate two independent sets of results.