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Published September 27, 2011 | Published + Supplemental Material
Journal Article Open

Dynamics and dissipation in enzyme catalysis

Abstract

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.

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.

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Published - Boekelheide2011p16028P_Natl_Acad_Sci_Usa.pdf

Supplemental Material - pnas.1106397108_SI.pdf

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