Group contribution method for thermodynamic analysis of complex metabolic networks

A new, to our knowledge, group contribution method based on the group contribution method of Mavrovouniotis is introduced for estimating the standard Gibbs free energy of formation (Δ_fG′°) and reaction (Δ_rG′°) in biochemical systems. Gibbs free energy contribution values were estimated for 74 distinct molecular substructures and 11 interaction factors using multiple linear regression against a training set of 645 reactions and 224 compounds. The standard error for the fitted values was 1.90 kcal/mol. Cross-validation analysis was utilized to determine the accuracy of the methodology in estimating Δ_rG′° and Δ_fG′° for reactions and compounds not included in the training set, and based on the results of the cross-validation, the standard error involved in these estimations is 2.22 kcal/mol. This group contribution method is demonstrated to be capable of estimating Δ_rG′° and Δ_fG′° for the majority of the biochemical compounds and reactions found in the iJR904 and iAF1260 genome-scale metabolic models of Escherichia coli and in the Kyoto Encyclopedia of Genes and Genomes and University of Minnesota Biocatalysis and Biodegradation Database. A web-based implementation of this new group contribution method is available free at http://sparta.chem-eng.northwestern.edu/cgi-bin/GCM/WebGCM.cgi.