Using constraints and their value for optimization of large ODE systems

We provide analytical tools to facilitate a rigorous assessment of the quality and value of the fit of a complex model to data. We use this to provide approaches to model fitting, parameter estimation, the design of optimization functions and experimental optimization. This is in the context where multiple constraints are used to select or optimize a large model defined by differential equations. We illustrate the approach using models of circadian clocks and the NF-kappa B signalling system.