Atomistic description of the relationship between protein dynamics and catalysis with transition path sampling

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Despite initial resistance, it has been increasingly accepted that protein dynamics plays a role in enzymatic catalysis. There have been two lines of research. Some works study slow conformational motions that are not coupled to the reaction coordinate, but guide the system towards catalytically competent conformations. Understanding at the atomistic level how this is accomplished has remained elusive except for a few systems. In this review we focus on fast sub-picosecond motions that are coupled to the reaction coordinate. The use of Transition Path Sampling has allowed us an atomistic description of how these rate-promoting vibrational motions are incorporated in the reaction mechanism. We will also show how we used insights from rate-promoting motions in protein design.

Original languageEnglish (US)
Title of host publicationNew Experimental Probes for Enzyme Specificity and Mechanism
EditorsJohn P. Richard, Graham R. Moran
PublisherAcademic Press Inc.
Pages319-340
Number of pages22
ISBN (Print)9780443152764
DOIs
StatePublished - Jan 2023

Publication series

NameMethods in Enzymology
Volume685

Keywords

  • Catalysis
  • Enzyme dynamics
  • Protein design
  • Transition path sampling

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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