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Dynamics and dissipation in enzyme catalysis

Boekelheide, Nicholas and Salomόn-Ferrer, Romelia and Miller, Thomas F., III (2011) Dynamics and dissipation in enzyme catalysis. Proceedings of the National Academy of Sciences of the United States of America, 108 (39). pp. 16159-16163. ISSN 0027-8424. PMCID PMC3182692.

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We use quantized molecular dynamics simulations to characterize the role of enzyme vibrations in facilitating dihydrofolate reductase hydride transfer. By sampling the full ensemble of reactive trajectories, we are able to quantify and distinguish between statistical and dynamical correlations in the enzyme motion. We demonstrate the existence of nonequilibrium dynamical coupling between protein residues and the hydride tunneling reaction, and we characterize the spatial and temporal extent of these dynamical effects. Unlike statistical correlations, which give rise to nanometer-scale coupling between distal protein residues and the intrinsic reaction, dynamical correlations vanish at distances beyond 4–6 Å from the transferring hydride. This work finds a minimal role for nonlocal vibrational dynamics in enzyme catalysis, and it supports a model in which nanometer-scale protein fluctuations statistically modulate—or gate—the barrier for the intrinsic reaction.

Item Type:Article
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URLURL TypeDescription DOIArticle CentralArticle
Boekelheide, Nicholas0000-0001-7296-9177
Miller, Thomas F., III0000-0002-1882-5380
Additional Information:© 2011 National Academy of Sciences. Freely available online through the PNAS open access option. Edited by Donald G. Truhlar, University of Minnesota, Minneapolis, MN, and approved August 5, 2011 (received for review April 21, 2011). Published online before print September 19, 2011. This work was supported by the National Science Foundation (NSF) CAREER Award (CHE-1057112) and computing resources at the National Energy Research Scientific Computing Center. Additionally, N.B. acknowledges an NSF graduate research fellowship, and T.F.M. acknowledges an Alfred P. Sloan Foundation fellowship. Author contributions: N.B., R.S.-F., and T.F.M. designed research, performed research, contributed new reagents/analytic tools, analyzed data, and wrote the paper.
Funding AgencyGrant Number
NSF Graduate Research FellowshipUNSPECIFIED
Alfred P. Sloan FoundationUNSPECIFIED
Subject Keywords:enzyme dynamics, hydrogen tunneling, path integral, ring polymer molecular dynamics
Issue or Number:39
PubMed Central ID:PMC3182692
Record Number:CaltechAUTHORS:20111018-111346185
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Official Citation:Nicholas Boekelheide, Romelia Salomón-Ferrer, and Thomas F. Miller III Dynamics and dissipation in enzyme catalysis PNAS 2011 108 (39) 16159-16163; published ahead of print September 19, 2011, doi:10.1073/pnas.1106397108
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:27279
Deposited By: Ruth Sustaita
Deposited On:18 Oct 2011 19:52
Last Modified:09 Mar 2020 13:18

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