Mixed quantum mechanical/molecular mechanical simulations of chemical reactions in solution and in enzymes by the...

We present a practical hybrid quantum mechanical/molecular mechanical approach to study chemical reactions in solution and in enzymes. In this method, referred to as the "Classical Trajectory Mapping" method, trajectories are calculated on the classical potential surfaces and, by using the classical surfaces as a reference state for the actual quantum mechanical ground state potential, the free energy profile of the chemical reaction is obtained by the free energy perturbation technique. This method was applied to proton-transfer reactions both in aqueous solution and in papain. The encouraging results indicate the applicability of our method to chemical reactions in the condensed phase and the biological systems.