Docking with DiffDock-L Preparation of the input files for docking For docking with DiffDock-L, fresh copies of the PDB files listed in the DUDE-Z were obtained directly from the PDB and loaded into the Schrödinger Platform (version 2021-1) for preprocessing using the Protein Preparation Wizard. The preparation steps included assigning bond orders, adding hydrogens, filling in missing side chains, removing water molecules, protonating residues at pH 7.4 using PROPKA, and restrainedly minimizing hydrogens using the OPLS4 force field. Docking Docking with DiffDock-L was executed using the "inference.py" script (part of DiffDock-L) to generate 30 poses for each ligand. All other arguments were kept at default values specified in "default_inference_args.yaml" (part of DiffDock-L). Further details are provided in the Supporting Information.