Difference between revisions of "Dynamic disorder in single enzyme kinetics: effects of conformational fluctuations"

Revision as of 09:44, 20 May 2010

Enzymes are dynamic entities: their conformations as well as catalytic activity fluctuate over time. A number of recent single-molecule experiments have shown that the catalytic activity of single enzymes can change with time, producing measurable kinetic effects, including time- dependent rate constants (a phenomenon known as dynamic disorder) and nonexponential waiting time distributions between successive turnover events. These effects are believed to be largely the result of slow conformational fluctuations between different states of the enzyme with distinct reactivities. A model of barrier crossing dynamics governed by fractional Gaussian noise and the generalized Langevin equation used to study the reaction kinetics of single enzymes subject to conformational fluctuations will be discussed. The direct application of Kramers's flux-over-population method to this model yields analytic expressions for the distribution of waiting times for barrier crossing. These expressions are found to reproduce the observed trends in recent experiments.

    Xie et. al have recently experimentally demonstrated that the Michelis Menten(MM) behavior 

of the average number of catalytic turnovers per unit time (for beta-galactosidase) still holds even in the presence of slow protein conformational fluctuations. The role of conformational dynamics on the dynamics of coupled enzymatic reactions (network) will be discussed. Our goal is to examine the limits in which such detailed dynamics can be simplified to a conventional rate- equation formalism by integration over conformational degrees of freedom, derive the relation between microscopic and macroscopic parameters and to investigate the validity of detailed balance conditions. Finally we investigate the influence of conformational fluctuations on networks nonlinear dynamics when conventional rate-equation formalism fails.