Vina and rDock yielded less overall enrichment. In some cases, AutoDock Vina and GOLD failed to dock the entire set of ligands (see Methods for details). In general, docking backends are not very sensitive to the choice of ligand embedder for the DEKOIS 2.0 targets. However, there are cases where the ligand embedder does have a significant effect on observed enrichment. For instance, AutoDock Vina with Corina and TautEnum for BCL2, Hybrid with LigPrep for RXRa, and rDock with RDKit and TautEnum for COX2, perform best within their ligand embedder series. Therefore, no single ligand embedder always performs best and while screening through 𝑛 different ligand embedders necessitate 𝑛 docking runs, increases in enrichment may identify a valuable docking configuration that otherwise would have been overlooked. Furthermore, no single docking backend performed best for all targets (compare COX2 Glide and AutoDock Vina ACHE for example). Alternatively, the goal may be to identify a reasonably good docking configuration with the highest throughput. Hybrid is particularly well suited for this owing to its speed and it may be the case that it also performs best or close to best performing as observed in the case of KIF11 and AR, respectively. Naturally, docking varies in performance for different target systems and ligand sets. The flexibility and ease of specifying different docking configurations and automating their execution and analysis demonstrates the value of a tool like DockStream.