Combined Quantum Mechanics and Molecular Mechanics Studies of Enzymatic Reaction Mechanisms

The combined quantum mechanics/molecular mechanics (QM/MM) methods have become a valuable tool in computational biochemistry and received versatile applications for studying the reaction mechanisms of enzymes. The approach combines the calculations of the electronic structure of the active site by QM, with modeling of the protein environment using MM force field, which allows the long-range electrostatics and steric effects on the enzyme reactivity to be accounted for. In this review, we review some key theoretical and computational aspects of the method and we also present some applications to particular enzymatic reactions such as tryptophan-7-halogenase, cyclooxygenase-1, and the epidermal growth factor receptor.