Construction of more reliable complex metabolic models without repeated solution of their constituent differential equations

A method is described for constructing metabolic models composed of many nonlinear stiff differential equations. The system being modeled is divided into subunits (where such division is impractical, forcing functions are used), and algebraic relationships for their behavior at an instant in time are derived. Most of the usual searches for correct model structure and parameter sets are then done with the set of these algebraic relationships at different time points, relatively few expensive differential equation solutions being required. The software used, the application to several models of cardiac metabolism, and the significance of models of this type are discussed.