Electronic and geometric structures of the blue copper site of azurin investigated byQM/MM hybrid calculations

Abstract

The electronic and geometric structures of the copper-binding site in a fully solvated azurinwere investigated using quantum mechanics (QM) and molecular mechanics (MM) hybridcalculations. Two types of computational models were applied to evaluate theeffects of the environment surrounding the active site. In model I, long-distanceelectrostatic interactions between QM region atoms and partial point chargesof the surrounding protein moieties and solvent water were calculated in a QMHamiltonian, for which the spin-unrestricted Hartree–Fock (UHF)/density functionaltheory (DFT) hybrid all-electron calculation with the B3LYP functional wasadopted. In model II, the QM Hamiltonian was not allowed to be polarized by thosepartial point charges. Models I and II provided different descriptions of the coppercoordination structure, particularly for the coordinative bonds including a largedipole. In fact, the Cu–O(Gly45) and Cu–S(Cys112) bonds are sensitive to thetreatment of long-distance electrostatic interactions in the QM Hamiltonian. Thissuggests that biological processes occurring in the active site are regulated by thesurrounding structures of protein and solvent, and therefore the effects of long-rangeelectrostatic interactions involved in the QM Hamiltonian are crucial for accuratedescriptions of electronic structures of the copper active site of metalloenzymes.