Fig. 3. Pre-reactive conformations from molecular dynamics simulations of (A) LmrR_M89X, (B) LmrR_M89X_D100E, (C) LmrR_M89X_W96E and (D–F) LmrR_M89X_V15E. Pre-reactive conformations are defined on the basis of the closeness of a water molecule to the β carbon of the substrate and the hydrogen-bonding to an aspartate or glutamate residue. Similar pre-reactive conformations are reached in 10% of the simulation by LmrR_M89X, 10% by LmrR_M89X_D100E, 91% LmrR_M89X_W96E and 31% by LmrR_M89X_V15E (Table S3†). The BpyA–Cu(ii)–1a force field parameters were calculated with programs MCPB for the bonding terms and RESP for atomic charges, both from the AMBER program package.⁵⁸ .