The DockM8 workflow (Figure ) was developed for Python 3.10 and the Ubuntu (version 20 and above) operating system, although it can be run in Windows Subsystem for Linux version 2 if required. Multiprocessing capabilities are integrated into DockM8, particularly during the docking and rescoring phases as these are the most resource-intensive. Allocation of individual processing runs across available CPU cores is managed by utilizing the multiprocessing or joblib libraries. DockM8 maintains a structured approach to file management, wherein a dedicated working directory houses the data generated after each step of ligand preparation, docking, clustering, and scoring procedures, thereby allowing subsequent analysis. A subset (see Supporting Information Section 1) of the DEKOIS 2.0 library (79 targets) was downloaded via the link provided in the original publication . The reference ligand and protein files were used as is in the DockM8 workflow. The docking library was generated by combining the actives and decoys into one SDF file and labeling each with 0 (for decoys) or 1 (for actives) to allow for the calculation of the performance metrics. The DockM8 conditions were set as follows :