Group Contribution Method for Thermodynamic Analysis of Complex Metabolic Networks

Abstract

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 (Delta(f)G'(o)) and reaction (Delta(r)G'(o)) 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 Delta(r)G'(o) and Delta(f)G'(o) 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 Delta(r)G'(o) and Delta(f)G'(o) 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.

Identification of metabolic engineering targets for the enhancement of 1,4-butanediol production in recombinant E. coli using large-scale kinetic models

“…Using the core stoichiometric model of E. coli metabolism we incorporated the thermodynamic constraints based on the available information on the Gibbs free energies of reactions (Alberty, 1994;Goldberg et al, 2004;Hadadi et al, 2015;Jankowski et al, 2008) and the available fluxomics and metabolomics data, and we performed TFA analysis to compute a thermodynamically feasible flux profile. Within this thermodynamically feasible flux profile each reaction is unidirectional, therefore its flux solution space is convex.…”

Assessment of the energy and exergy efficiencies of farm to fork grain cultivation and bread making processes in Turkey and Germany

“…Some of the thermodynamic properties were not readily available in the literature, and estimated with the group contribution method based on the molecular structures (Table 5). In accordance with this method, the molecular structure of a compound is decomposed into a set of smaller molecular substructures [60] and then the sum of the thermodynamic properties of these substructures are added up to estimate that of the structure.…”

Predicting network functions with nested patterns

“…Yet, the reaction direction score S can be interpreted as a quantitative approximation of the reactions' standard Gibbs free energy changes, D r G°(up to a scaling factor; see Supplementary Methods). Because few experimental thermodynamic data are available 28 , reaction energies of chemical reactions in general are often estimated by group contribution methods that consider the additive reaction energies of chemical sub-structures 35 . Reaction directions then depend on these energies and on metabolite concentrations.…”