TY - JOUR
T1 - A Bayesian Analysis of Steady–State Enzyme Data leads to Estimates of Rate Constants and Uncertainties in a Multi-Step Reaction<sup>†</sup>
JF - bioRxiv
DO - 10.1101/2021.08.04.454956
SP - 2021.08.04.454956
AU - Barr, Ian
Y1 - 2021/01/01
UR - http://biorxiv.org/content/early/2021/08/06/2021.08.04.454956.abstract
N2 - The microscopic rate constants that govern an enzymatic reaction are only directly measured under certain experimental set-ups, such as stopped flow, continuous flow, or temperature-jump assays; the majority of enzymology proceeds from steady state conditions which leads to a set of easily–observable parameters such as kcat, KM, and observed Kinetic Isotope Effects (Dkcat). This paper further develops a model from Toney (2013) to estimate microscopic rate constants from steady-state data for a set of reversible, four–step reactions. This paper uses the Bayesian modeling software Stan, and demonstrates the benefits of Bayesian data analysis in the estimation of these rate constants. In contrast to the optimization methods employed often in the estimation of kinetic constants, a Bayesian treatment is more equipped to estimate the uncertainties of each parameter; sampling from the posterior distribution using Hamiltonian Monte Carlo immediately gives parameter estimates as mean or median of the posterior, and also confidence intervals that express the uncertainty of each parameter.Competing Interest StatementThe authors have declared no competing interest.
ER -