Convergence of Theory and Experiment on the Role of Preorganization, Quantum Tunneling, and Enzyme Motions into Flavoenzyme-Catalyzed Hydride Transfer

Research output: Contribution to journalArticle

  • External authors:
  • Manuel Delgado
  • Stefan Gorlich
  • James E Longbotham
  • Vicent Moliner
  • Iñaki Tuñón


Hydride transfer is one of the most common reactions catalyzed by enzymatic systems, and it has become an object of study because of possible significant quantum tunneling effects. In the present work, we provide a combination of theoretical QM/MM simulations and experimental measurements of the rate constants and kinetic isotopic effects (KIEs) for the hydride transfer reaction catalyzed by morphinone reductase, MR. Quantum mechanical tunneling coefficients, computed in the framework of variational transition-state theory, play a significant role in this reaction, reaching values of 23.8 ± 5.5 for the lightest isotopologue—one of the largest values reported for enzymatic systems. This prediction is supported by the agreement between the theoretically predicted rate constants and the corresponding experimental values. Simulations indicate that the role of protein motions can be satisfactorily described as equilibrium fluctuations along the reaction coordinate, in line with a high degree of preorganization displayed by this enzyme.

Bibliographical metadata

Original languageEnglish
Pages (from-to)3190–3198
JournalACS Catalysis
Early online date27 Mar 2017
StatePublished - 2017