Estimation of kinetic parameters in a structured yeast model using regularisation

In this work, a procedure for estimating kinetic parameters in biochemicall y structured models was developed. The approach is applicable when the stru cture of a kinetic model has been set up and the kinetic parameters should be estimated. The procedure consists of five steps. First, initial values w ere found in or calculated from literature. Hereafter using sensitivity ana lysis the most sensitive parameters were identified. In the third step phys iological knowledge was combined with the parameter sensitivities to manual ly tune the most sensitive parameters. In step four, a global optimisation routine was applied for simultaneous estimation of the most sensitive param eters identified during the sensitivity analysis. Regularisation was includ ed in the simultaneous estimation to reduce the effect of insensitive param eters. Finally, confidence intervals for the estimated parameters were calc ulated. This parameter estimation approach was demonstrated on a biochemica lly structured yeast model. containing 11 reactions and 37 kinetic constant s as a case study. (C) 2001 Elsevier Science B.V. All rights reserved.