The AMBER parameters for radical Gly829 were taken from Barone et al . The BSS models were solvated with explicit water molecules (10 Å radius around the protein, 23,324 or 24,215 water molecules, respectively for holo-and apoenzyme) and the calculations were conducted in a periodic-boundaries box (119.6 Å × 86.3 Å × 96.8 Å). The AMBER parameters for radical Cys493 were derived according to standard protocols . All AMBER parameters of enzyme ligands and non-standard residues were provided in Supplementary Information.