title: A metabolic network analysis & NMR experiment design tool with user interface-driven model construction for depth-first search analysis.
abstract: A Windows program for metabolic engineering analysis and experimental design has been developed. A graphical user interface enables the pictorial, "on-screen" construction of a metabolic network. Once a model is composed, balance equations are automatically generated. Model construction, modification and information exchange between different users is thus considerably simplified. For a given model, the program can then be used to predict all the extreme point flux distributions that optimize an objective function while satisfying balances and constraints by using a depth-first search strategy. One can also find the minimum reaction set that satisfies different conditions. Based on the identified flux distributions or linear combinations, the user can simulate the NMR and GC/MS spectra of selected signal molecules. Alternately, spectra vectorization allows for the automated optimization of labeling experiments that are intended to distinguish between different, yet plausible flux extreme point distributions. The example provided entails predicting the flux distributions associated with deleting pyruvate kinase and designing 13C NMR experiments that can maximally discriminate between the flux distributions.
authors.affiliation: Department of Chemical Engineering, The University of Pittsburgh, USA.
authors.forename: T
authors.initials: T
authors.lastname: Zhu
authors.forename: C
authors.initials: C
authors.lastname: Phalakornkule
authors.forename: S
authors.initials: S
authors.lastname: Ghosh
authors.forename: I E
authors.initials: IE
authors.lastname: Grossmann
authors.forename: R R
authors.initials: RR
authors.lastname: Koepsel
authors.forename: M M
authors.initials: MM
authors.lastname: Ataai
authors.forename: M M
authors.initials: MM
authors.lastname: Domach
mesh_terms: D003198:Computer Simulation; D015195:Drug Design; D004926:Escherichia coli / Q000201:enzymology; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008660:Metabolism / Q000502:physiology*; D008954:Models, Biological; D008956:Models, Chemical; D009097:Multienzyme Complexes / Q000378:metabolism; D015202:Protein Engineering / Q000379:methods*; D040901:Proteomics / Q000379:methods*; D011770:Pyruvate Kinase / Q000378:metabolism; D012107:Research Design; D014584:User-Computer Interface
chemical_list: D009097:Multienzyme Complexes; D018698:Glutamic Acid; D011770:Pyruvate Kinase; D005947:Glucose