Indistinguishability and identifiability of kinetic models for the MurC reaction in peptidoglycan biosynthesis

Abstract An important question in Systems Biology is the design of experiments that enable discrimination between two (or more) competing chemical pathway models or biological mechanisms. In this paper analysis is performed between two different models describing the kinetic mechanism of a three-sub...

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Bibliographic Details
Published in:Computer methods and programs in biomedicine 2011-11, Vol.104 (2), p.70-80
Main Authors: Hattersley, J.G, Pérez-Velázquez, J, Chappell, M.J, Bearup, D, Roper, D, Dowson, C, Bugg, T, Evans, N.D
Format: Article
Language:English
Subjects:
Biomedical systems
Experiment design
Identifiability
Indistinguishability
Internal Medicine
Kinetics
Models, Theoretical
MurC
Other
Parameter identification
Peptidoglycan - biosynthesis
Systems Biology
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Summary:Abstract An important question in Systems Biology is the design of experiments that enable discrimination between two (or more) competing chemical pathway models or biological mechanisms. In this paper analysis is performed between two different models describing the kinetic mechanism of a three-substrate three-product reaction, namely the MurC reaction in the cytoplasmic phase of peptidoglycan biosynthesis. One model involves ordered substrate binding and ordered release of the three products; the competing model also assumes ordered substrate binding, but with fast release of the three products. The two versions are shown to be distinguishable; however, if standard quasi-steady-state assumptions are made distinguishability cannot be determined. Once model structure uniqueness is ensured the experimenter must determine if it is possible to successfully recover rate constant values given the experiment observations, a process known as structural identifiability. Structural identifiability analysis is carried out for both models to determine which of the unknown reaction parameters can be determined uniquely, or otherwise, from the ideal system outputs. This structural analysis forms an integrated step towards the modelling of the full pathway of the cytoplasmic phase of peptidoglycan biosynthesis.
ISSN:0169-2607
1872-7565
DOI:10.1016/j.cmpb.2010.07.009