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Computational Methods: Modeling of Reactivity in Zn-Containing Enzymes

  1. Jon I. Mujika,
  2. Adrian J. Mulholland,
  3. Jeremy N. Harvey

Published Online: 15 SEP 2009

DOI: 10.1002/0470862106.ia627

Encyclopedia of Inorganic Chemistry

Encyclopedia of Inorganic Chemistry

How to Cite

Mujika, J. I., Mulholland, A. J. and Harvey, J. N. 2009. Computational Methods: Modeling of Reactivity in Zn-Containing Enzymes. Encyclopedia of Inorganic Chemistry. .

Author Information

  1. University of Bristol, Bristol, UK

Publication History

  1. Published Online: 15 SEP 2009


Computation is increasingly well placed to offer insight into a range of structural and spectroscopic properties of Zn-containing enzymes, as well as into their reactivity. The latter aspect is the focus of this article. Molecular dynamics simulations provide insight into substrate binding and active-site relaxation around the metal and substrate. A significant challenge in such studies is the representation of the zinc center. Quantum mechanical methods, either on their own using small active-site models, or for whole enzymes using hybrid techniques, provide insight into reaction paths and hence into transition states and intermediates. Examples of these applications are reviewed for carbonic anhydrase, carboxypeptidase A, thermolysin, type B β-lactamase, and farnesyltransferase.


  • quantum chemistry;
  • computational enzymology;
  • zinc proteases;
  • QM/MM;
  • DFT;
  • molecular mechanics;
  • reaction mechanisms;
  • biomolecular simulation