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Indistinguishability and identifiability of kinetic models for the MurC reaction in peptidoglycan biosynthesis
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Hattersley, J. G. (John G.), PérezVelázquez, J., Chappell, M. J. (Michael J.), Bearup, Daniel James, Roper, David I., Dowson, Christopher G., Bugg, Tim and Evans, N. D.. (2011) Indistinguishability and identifiability of kinetic models for the MurC reaction in peptidoglycan biosynthesis. Computer Methods and Programs in Biomedicine, Vol.104 (No.2). pp. 7080. ISSN 01692607

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Official URL: http://dx.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 threesubstrate threeproduct 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 steadystate assumptions are made distinguishability can not 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:  Journal Article 

Subjects:  Q Science > QH Natural history > QH301 Biology 
Divisions:  Faculty of Science > Life Sciences (2010 ) > Biological Sciences ( 2010) Faculty of Science > Chemistry Faculty of Science > Engineering Faculty of Science > Life Sciences (2010 ) 
Library of Congress Subject Headings (LCSH):  Peptidoglycans  Synthesis  Mathematical models, Systems biology  Mathematical models, Experimental design 
Journal or Publication Title:  Computer Methods and Programs in Biomedicine 
Publisher:  Elsevier BV 
ISSN:  01692607 
Date:  2011 
Volume:  Vol.104 
Number:  No.2 
Page Range:  pp. 7080 
Identification Number:  10.1016/j.cmpb.2010.07.009 
Status:  Peer Reviewed 
Publication Status:  Published 
Access rights to Published version:  Restricted or Subscription Access 
Funder:  Engineering and Physical Sciences Research Council (EPSRC) 
Grant number:  EP/E057535/1 
Version or Related Resource:  This item was also submitted to the 7th IFAC Symposium on Modelling and Control in Biomedical Systems, Aalborg, Denmark, Aug 12  14, 2009. 
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URI:  http://wrap.warwick.ac.uk/id/eprint/40524 
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