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

The electronic and geometric structures of the copper-binding site in a fully solvated azurin were investigated using quantum mechanics (QM) and molecular mechanics (MM) hybrid calculations. Two types of computational models were applied to evaluate the effects of the environment surrounding the active site. In model I, long-distance electrostatic interactions between QM region atoms and partial point charges of the surrounding protein moieties and solvent water were calculated in a QM Hamiltonian, for which the spin-unrestricted Hartree-Fock (UHF)/density functional theory (DFT) hybrid all-electron calculation with the B3LYP functional was adopted. In model II, the QM Hamiltonian was not allowed to be polarized by those partial point charges. Models I and II provided different descriptions of the copper coordination structure, particularly for the coordinative bonds including a large dipole. In fact, the Cu-O(Gly45) and Cu-S(Cys112) bonds are sensitive to the treatment of long-distance electrostatic interactions in the QM Hamiltonian. This suggests that biological processes occurring in the active site are regulated by the surrounding structures of protein and solvent, and therefore the effects of long-range electrostatic interactions involved in the QM Hamiltonian are crucial for accurate descriptions of electronic structures of the copper active site of metalloenzymes.