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Indistinguishability and identifiability of kinetic models for the MurC reaction in peptidoglycan biosynthesis
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Hattersley, John G., Pérez-Velázquez, J., Chappell, M. J. (Michael J.), Bearup, Daniel James, Roper, David I., Dowson, Christopher G., Bugg, Tim and Evans, Neil 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. 70-80. doi:10.1016/j.cmpb.2010.07.009 ISSN 01692607.
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WRAP_Evans_9871863-es-131211-murcpaperjhattersley_final.pdf - Accepted Version - Requires a PDF viewer. Download (321Kb) |
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 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 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 | ||||
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Subjects: | Q Science > QH Natural history > QH301 Biology | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) > Biological Sciences ( -2010) Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Engineering > Engineering Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) |
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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 | ||||
Official Date: | 2011 | ||||
Dates: |
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Volume: | Vol.104 | ||||
Number: | No.2 | ||||
Page Range: | pp. 70-80 | ||||
DOI: | 10.1016/j.cmpb.2010.07.009 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access | ||||
Date of first compliant deposit: | 18 December 2015 | ||||
Date of first compliant Open Access: | 18 December 2015 | ||||
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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