Quantum mechanical tunneling in methylamine dehydrogenase

We report a calculation for a trideuteration kinetic isotope effect (KIE) f or the proton transfer step in the oxidation of methylamine by the quinopro tein methylamine dehydrogenase (MADH). The potential field includes 11025 a toms, and the dynamics are based on a quantum mechanical/molecular mechanic al (QM/MM) direct dynamics simulation and canonical variational transition state theory with small-curvature multidimensional tunneling contributions. About 1% of the reaction occurs by overbarrier processes, with the rest du e to tunneling, and the calculated KIE is reduced to 5.9 when we omit tunne ling. This provides the most striking evidence yet for the contribution of tunneling processes to enzymatic reactions at physiological temperatures. ( C) 2001 Published by Elsevier Science B.V.