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

Hattersley, J.G., Pérez-Velázquez, J., Chappell, M.J., Bearup, Daniel, Roper, D., Dowson, C., Bugg, T., Evans, N.D. (2010) Indistinguishability and identifiability of kinetic models for the MurC reaction in peptidoglycan biosynthesis. Computer Methods and Programs in Biomedicine, 104 (2). pp. 70-80. ISSN 0169-2607. (doi:10.1016/j.cmpb.2010.07.009) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
https://doi.org/10.1016/j.cmpb.2010.07.009

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.

Item Type: Article
DOI/Identification number: 10.1016/j.cmpb.2010.07.009
Additional information: cited By 3
Uncontrolled keywords: Indistinguishability; Identifiability; Experiment design; MurC; Biomedical systems; Parameter identification
Subjects: Q Science > QA Mathematics (inc Computing science)
Q Science > QA Mathematics (inc Computing science) > QA276 Mathematical statistics
Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Faculties > Sciences > School of Mathematics Statistics and Actuarial Science
Faculties > Sciences > School of Mathematics Statistics and Actuarial Science > Applied Mathematics
Depositing User: Daniel Bearup
Date Deposited: 30 Nov 2017 11:21 UTC
Last Modified: 29 May 2019 19:47 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/64323 (The current URI for this page, for reference purposes)
Bearup, Daniel: https://orcid.org/0000-0001-8524-7659
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