Globally optimised 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 & Tyson. In a recent publication, we showed that a gradient-based optimisation algorithm finds a locally optimal parameter set quite close to the 'Marlovits' estimates. In this paper, we combine global and local optimisation 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.
Zwolak
J W
JW
Department of Computer Science, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061-0106, USA. jzwolak@vt.edu
Tyson
J J
JJ
Watson
L T
LT
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002457:Cell Extracts; D003198:Computer Simulation; D003593:Cytoplasm / Q000378:metabolism; D005246:Feedback / Q000502:physiology; D008938:Mitosis / Q000502:physiology*; D008954:Models, Biological; D011898:Ranidae / Q000033:anatomy & histology* / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D018797:Cell Cycle Proteins; D002457:Cell Extracts