Electrostatics as the Driving Force Behind the Catalytic Function of the Monoamine Oxidase A Enzyme Confirmed by Quantum Computations

While the function of enzymes has been well-known to researchers for decades, the driving force behind it is still a hotly debated topic. Herein, we report significant evidence for electrostatics being that driving force, using a simple, computationally inexpensive, multiscale model of monoamine oxidase A and phenylethylamine. We found that electrostatics provided by the enzyme substantially enhances the reaction by all the considered criteria (lowering the energy barrier, increasing charge transfer, decreasing the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) gap, increasing the dipole moment). The catalytic effect can be rationalized by the stabilizing interaction between the dipole moment of the reacting moiety and the electric field exerted by the charged environment. Both the dipole moment and the electric field are perceivably larger in the transition state as compared to the state of reactants; hence the transition state is stabilized to a larger extent and better solvated than the state of reactants, thereby lowering the barrier. Our findings support the view that catalysis in enzymes originates from preorganized electrostatics.