Group Contribution Method for Thermodynamic Analysis of Complex Metabolic Networks

• Published in: Biophysical journal 2008-08, Vol.95 (3), p.1487-1499
• Main Authors: Jankowski, Matthew D., Henry, Christopher S., Broadbelt, Linda J., Hatzimanikatis, Vassily
• Format: Article
• Language: English
• Subjects: Biochemistry; Bioenergetics; Chemical compounds; Chemical reactions; Computer Simulation; Estimating; Genomes; Gibbs free energy; Mathematical models; Models, Biological; Molecular biology; Proteome - metabolism; Signal Transduction - physiology; Standard error; Thermodynamics; Training
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1529/biophysj.107.124784

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 f G′°) and reaction (Δ r G′°) 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 r G′° and Δ f G′° 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 r G′° and Δ f G′° 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.