Diverse metabolic model parameters generate similar methionine cycle dynamics. Author Matthew Piazza, Xiao-Jiang Feng, Joshua Rabinowitz, Herschel Rabitz Publication Year 2008 Type Journal Article Abstract Parameter estimation constitutes a major challenge in dynamic modeling of metabolic networks. Here we examine, via computational simulations, the influence of system nonlinearity and the nature of available data on the distribution and predictive capability of identified model parameters. Simulated methionine cycle metabolite concentration data (both with and without corresponding flux data) was inverted to identify model parameters consistent with it. Thousands of diverse parameter families were found to be consistent with the data to within moderate error, with most of the parameter values spanning over 1000-fold ranges irrespective of whether flux data was included. Due to strong correlations within the extracted parameter families, model predictions were generally reliable despite the broad ranges found for individual parameters. Inclusion of flux data, by strengthening these correlations, resulted in substantially more reliable flux predictions. These findings suggest that, despite the difficulty of extracting biochemically accurate model parameters from system level data, such data may nevertheless prove adequate for driving the development of predictive dynamic metabolic models. Keywords Animals, Metabolic Networks and Pathways, Systems Biology, Models, Biological, Computer Simulation, Methionine, Homeostasis, Enzymes Journal J Theor Biol Volume 251 Issue 4 Pages 628-39 Date Published 04/2008 Alternate Journal J. Theor. Biol. Google ScholarBibTeXEndNote X3 XML