Directed Evolution as a Probe of Rate Promoting Vibrations Introduced via Mutational Change

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3 Scopus citations

Abstract

In this article, we study with transition path sampling and reaction coordinate analysis how directed evolution in the Kemp eliminase family of artificial enzymes makes differential use of rapid rate promoting vibrations as a component of their chemical mechanism. Even though this family was initially created by placing the expected active site in a fixed protein matrix, we find a shift from largely static to more dynamic active sites that make use of donor-acceptor compression as the evolutionary process proceeds. We see that this introduction of dynamics significantly shifts the order of processes in the reaction. We also suggest that the lack of "design for dynamics" may help explain the relatively low proficiency of such designed enzymes.

Original languageEnglish (US)
Pages (from-to)3289-3298
Number of pages10
JournalBiochemistry
Volume57
Issue number23
DOIs
StatePublished - Jun 12 2018

ASJC Scopus subject areas

  • Biochemistry

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