Protein dynamics and enzyme catalysis: the ghost in the machine?
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Updated: May 22, 2026

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
Published on: January 16, 2016
David R Glowacki1, Jeremy N Harvey, Adrian J Mulholland
1Centre for Computational Chemistry, School of Chemistry, University of Bristol, Bristol, U.K. David.R.Glowacki@bristol.ac.uk
Abstract:
One of the most controversial questions in enzymology today is whether protein dynamics are significant in enzyme catalysis. A particular issue in these debates is the unusual temperature-dependence of some kinetic isotope effects for enzyme-catalysed reactions. In the present paper, we review our recent model [Glowacki, Harvey and Mulholland (2012) Nat. Chem. 4, 169-176] that is capable of reproducing intriguing temperature-dependences of enzyme reactions involving significant quantum tunnelling. This model relies on treating multiple conformations of the enzyme-substrate complex. The results show that direct 'driving' motions of proteins are not necessary to explain experimental observations, and show that enzyme reactivity can be understood and accounted for in the framework of transition state theory.
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