Globally Optimized Parameters for a Model of Mitotic Control in Frog Egg Extracts

DNA synthesis and nuclear division in the developing frog egg are controlled by fluctuations in the activity of M-phase promoting factor (MPF). The biochemical mechanism of MPF regulation is most easily studied in cytoplasmic extracts of frog eggs, for which careful experimental studies of the kinetics of phosphorylation and dephosphorylation of MPF and its regulators have been made. In 1998 Marlovits et al. used these data sets to estimate the kinetic rate constants in a mathematical model of the control system originally proposed by Novak and Tyson. In a recent publication, we showed that a gradient-based optimization algorithm finds a locally optimal parameter set quite close to the Marlovits estimates. In this paper, we combine global and local optimization strategies to show that the refined Marlovits parameter set, with one minor but significant modification to the Novak-Tyson equations, is the unique, best-fitting solution to the parameter estimation problem.