Mixed quantum-classical simulation of the hydride transfer reaction catalyzed by dihydrofolate reductase based on a mapped system-harmonic bath model.

Abstract

The hydride transfer reaction catalyzed by dihydrofolate reductase is studied using a recently developed mixed quantum-classical method to investigate the nuclear quantum effects on the reaction. Molecular dynamics simulation is first performed based on a two-state empirical valence bond potential to map the atomistic model to an effective double-well potential coupled to a harmonic bath. In the mixed quantum-classical simulation, the hydride degree of freedom is quantized, and the effective harmonic oscillator modes are treated classically. It is shown that the hydride transfer reaction rate using the mapped effective double-well/harmonic-bath model is dominated by the contribution from the ground vibrational state. Further comparison with the adiabatic reaction rate constant based on the Kramers theory confirms that the reaction is primarily vibrationally adiabatic, which agrees well with the high transmission coefficients found in previous theoretical studies. The calculated kinetic isotope effect is also consistent with the experimental and recent theoretical results.