Valence bond and enzyme catalysis: A time to break down and a time to build up

Avital Sharir-Ivry, Rajapandian Varatharaj, Avital Shurki*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Understanding enzyme catalysis and developing ability to control of it are two great challenges in biochemistry. A few successful examples of computational-based enzyme design have proved the fantastic potential of computational approaches in this field, however, relatively modest rate enhancements have been reported and the further development of complementary methods is still required. Herein we propose a conceptually simple scheme to identify the specific role that each residue plays in catalysis. The scheme is based on a breakdown of the total catalytic effect into contributions of individual protein residues, which are further decomposed into chemically interpretable components by using valence bond theory. The scheme is shown to shed light on the origin of catalysis in wild-type haloalkane dehalogenase (wt-DhlA) and its mutants. Furthermore, the understanding gained through our scheme is shown to have great potential in facilitating the selection of non-optimal sites for catalysis and suggesting effective mutations to enhance the enzymatic rate.

Original languageAmerican English
Pages (from-to)7159-7169
Number of pages11
JournalChemistry - A European Journal
Issue number19
StatePublished - 18 Mar 2015

Bibliographical note

Publisher Copyright:
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


  • computational chemistry
  • enzyme catalysis
  • enzyme design
  • quantum mechanics
  • valence bond theory


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