Quantum-classical simulation methods for hydrogen transfer in enzymes: a case study of dihydrofolate reductase. Journal   Current opinion in structural biology. Citation   Curr Opin Struct Biol. 14(2):192-201 Publication date   2004 Apr Authors   Hammes-Schiffer S Grant agencies   National Institute of General Medical Sciences Grants   NIGMS GM56207 Abstract   A variety of theoretical approaches have been used to investigate hydrogen transfer in enzymatic reactions. The free energy barriers for hydrogen transfer in enzymes have been calculated using classical molecular dynamics simulations in conjunction with quantum mechanical/molecular mechanical and empirical valence bond potentials. Nuclear quantum effects have been included with several different approaches. Applications of these approaches to hydride transfer in dihydrofolate reductase are consistent with experimental measurements and provide significant insight into the protein conformational changes that facilitate the hydride transfer reaction.