Catalytic reactions at the molecular level do not proceed deterministically. Fluctuations of both quantum mechanical and thermal origin, termed as molecular noise, are inherent to reactions
catalyzed by individual enzyme molecules or nanoparticles. These impart stochasticity to each step in the catalytic mechanism, such that neither the lifetime of a given state and nor the state to which it transits can be known with certainty. Advances in experimental techniques have now made it possible to measure, with precision, the effect of molecular noise in enzyme or nanoparticle catalyses, involving a single enzyme / nanoparticle and numerous substrates.Various conformational fluctuations of the enzymes as well as surface restructuring dynamics of the nanoparticles that are hidden in bulk kinetic measurements can be revealed from single molecular kinetics measurements and a lot of subpopulation of particles that do not play much role in the bulk kinetic data can be discerned through this. [1-3]
At the single molecule level, stochasticity arises due to molecular discreteness, where each state in the reaction mechanism is considered discrete. Each discrete state is specified by the joint
probability distribution, the time evolution of which follows chemical master equation(CME). [4,5] This is in contrast to classical chemical kinetics, where deterministic mass action kinetics governs the time evolution of the concentrations of various species. In this seminar, theoretical modeling based on the CME, which assumes each elementary step of the reaction mechanism as memoryless will be shown to extract catalytic mechanisms and rate parameters from
experimental data. How statistical measures derived from CME can be used to quantify cooperativity at the molecular level will be discussed. Furthermore, how this formalism can be used to understand the non-classical behavior of stochastic enzyme-inhibitor and mnemonic enzymatic networks will be discussed.
References:
[1] B. P. English, W. Min, A. M. van Oijen, K. T. Lee, G. Luo, H. Sun, B. J. Cherayil, S. C.
Kou, and X. S. Xie, Nat. Chem. Biol. 2, 87 (2006).
[2] W. Xu, J. S. Kong, Y.-T. E. Yeh, and P. Chen, Nat. Mater. 7, 992 (2008).
[3] H. M. Piwonski, M. Goomanovsky, D. Bensimon, A. Horovitz, and G. Haran, Proc Natl
Acad Sci USA 22, 1437 (2012).
[4] D. T. Gillespie, Annu. Rev. Phys. Chem. 58, 35 (2007).
[5] J. R. Moffitt and C. Bustamante, FEBS J. 281, 498 (2014).