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Photo Lynn Kamerlin

Lynn Kamerlin

Professor

Photo Lynn Kamerlin

Harnessing Conformational Plasticity to Generate Designer Enzymes

Author

  • Rory M Crean
  • Jasmine M Gardner
  • Shina C L Kamerlin

Summary, in English

Recent years have witnessed an explosion of interest in understanding the role of conformational dynamics both in the evolution of new enzymatic activities from existing enzymes and in facilitating the emergence of enzymatic activity de novo on scaffolds that were previously non-catalytic. There are also an increasing number of examples in the literature of targeted engineering of conformational dynamics being successfully used to alter enzyme selectivity and activity. Despite the obvious importance of conformational dynamics to both enzyme function and evolvability, many (although not all) computational design approaches still focus either on pure sequence-based approaches or on using structures with limited flexibility to guide the design. However, there exist a wide variety of computational approaches that can be (re)purposed to introduce conformational dynamics as a key consideration in the design process. Coupled with laboratory evolution and more conventional existing sequence- and structure-based approaches, these techniques provide powerful tools for greatly expanding the protein engineering toolkit. This Perspective provides an overview of evolutionary studies that have dissected the role of conformational dynamics in facilitating the emergence of novel enzymes, as well as advances in computational approaches that allow one to target conformational dynamics as part of enzyme design. Harnessing conformational dynamics in engineering studies is a powerful paradigm with which to engineer the next generation of designer biocatalysts.

Publishing year

2020-07-01

Language

English

Pages

11324-11342

Publication/Series

Journal of the American Chemical Society

Volume

142

Issue

26

Document type

Journal article review

Publisher

The American Chemical Society (ACS)

Keywords

  • Biocatalysis
  • Enzymes/chemistry
  • Humans
  • Molecular Dynamics Simulation
  • Protein Conformation
  • Protein Engineering

Status

Published

ISBN/ISSN/Other

  • ISSN: 1520-5126