For Corina with TautEnum (tool to enumerate tautomers and protonation states, version 2.0.0), default parameters were used. For LigPrep, default parameters were used except for Epik, for which the target pH was set to 7.0 with a tolerated range of ± 2.0. 30 The ligand energies were minimized using the OPSL3e force-field. For RDKit (version 2020.09.3) with TautEnum, default parameters were used except for the number of maximum iterations, which was set to 600 (for Universal Force-Field, UFF) to ensure convergence for all compounds. All prepared ligands were saved as SDF files and also stored internally in DockStream as RDKit molecules for subsequent docking.