Computer simulations of quantum tunnelling in enzyme-catalysed hydrogen transfer reactions

Kara E Ranaghan, Adrian J Mulholland

Research output: Contribution to journalArticle (Academic Journal)peer-review

15 Citations (Scopus)


Transfer of hydrogen as a proton, hydride or hydrogen atom is an important step in many enzymic reactions. Experiments show kinetic isotope effects (KIEs) for some enzyme-catalysed hydrogen transfer reactions that deviate significantly from the limits imposed by considering the differences in mass of the isotopes alone (i.e. the semiclassical limit). These KIEs can be explained if the transfer of the hydrogen species occurs via a quantum mechanical tunnelling mechanism. The unusual temperature dependence of some KIEs has led to suggestions that enzymes have evolved to promote tunnelling through dynamics - a highly controversial hypothesis. Molecular simulations have a vital role in resolving these questions, providing a level of detail of analysis not possible through experiments alone. Here, we review computational molecular modelling studies of quantum tunnelling in enzymes, in particular focusing on the enzymes soybean lipoxygenase-1 (SLO-1), dihydrofolate reductase (DHFR), methylamine dehydrogenase (MADH) and aromatic amine dehydrogenase (AADH) to illustrate the current controversy regarding the importance of quantum effects in enzyme catalysis.

Original languageEnglish
Pages (from-to)78-97
Number of pages20
JournalInterdisciplinary sciences, computational life sciences
Issue number1
Publication statusPublished - Mar 2010


  • Algorithms
  • Amines
  • Biochemistry
  • Computer Simulation
  • Enzymes
  • Hydrogen
  • Kinetics
  • Lipoxygenase
  • Models, Chemical
  • Models, Molecular
  • Models, Statistical
  • Oxidoreductases
  • Oxidoreductases Acting on CH-NH Group Donors
  • Quantum Theory
  • Tetrahydrofolate Dehydrogenase


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