(653e) Transition State Theory and Dynamics in the Rate Promoting Vibrations Model of Enzyme Catalysis

The power of transition state theory (TST) for understanding enzymes has recently been demonstrated by its use in the design and synthesis of highly active de novo enzymes. However, dynamics can influence reaction rates, and some studies of rate-promoting vibrations (RPVs) claim that dynamical theories beyond TST are essential for enzymes with RPVs. The RPV model of enzyme catalysis [Antoniou et al. J. Chem. Phys. 2004, 121, 6442], was devised to illustrate the importance of theories beyond TST for studies of enzymes. On the basis of the RPV model, many later simulation results were interpreted as dynamical effects, but there has been no comparison to a TST calculation. Our findings show that dynamical effects do slow the kinetics. However, the RPV and the bath are not directly coupled, and the lack of coupling leads to unphysical correlations in the RPV dynamics that extend beyond 100ps. Additionally, earlier studies of the RPV model show a narrow time scale separation because of a small 5kT barrier. We show that the information computed for a standard harmonic TST calculation is sufficient to identify special RPVs amongst other more mundane bath variables. In the framework of TST the RPV influences the activation energy through early pre-organization and late re-organization processes, irrespective of the RPV dynamics. Our findings support the view that TST (with tunneling corrections for H-transfers) is adequate for understanding most enzymatic mechanisms.

B. Peters, J. Chem. Theory and Comp. (2010) in press