Flexibility of just the reactive Cys145 residue during cross-docking did not improve the success rate (26%). Flexibility of all residues of the target structure (PDB ID 7c7p) which were situated at a distance below 2 Å to one of the ligands after protein superimposition and therefore susceptible to generate clashes (11 amino acids, Supporting Information, Figure ), also did not improve the success rate (25%). These results may be due to the fact that the cavity of the target structure is wide open and does not generate many clashes with different ligands.