Quantum mechanical tunneling in methylamine dehydrogenase

Cristóbal Alhambra, Maria Luz Sánchez, José Corchado, Jiali Gao, Donald G. Truhlar

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We report a calculation for a trideuteration kinetic isotope effect (KIE) for the proton transfer step in the oxidation of methylamine by the quinoprotein methylamine dehydrogenase (MADH). The potential field includes 11025 atoms, and the dynamics are based on a quantum mechanical/molecular mechanical (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 due to tunneling, and the calculated KIE is reduced to 5.9 when we omit tunneling. This provides the most striking evidence yet for the contribution of tunneling processes to enzymatic reactions at physiological temperatures.

Original languageEnglish (US)
Pages (from-to)512-518
Number of pages7
JournalChemical Physics Letters
Issue number4-6
StatePublished - Oct 26 2001

Bibliographical note

Funding Information:
We thank the National Institutes of Health and the National Science Foundation for partial support of this research.


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