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Modelling and Dynamic Behaviour of Eif2 Dependent Regulatory System With Disturbances

Khan, MF; Spurgeon, SK; Yan, XG; (2018) Modelling and Dynamic Behaviour of Eif2 Dependent Regulatory System With Disturbances. IEEE Transactions on Nanobioscience 10.1109/TNB.2018.2873027. (In press). Green open access

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Abstract

Eukaryotic initiation factor 2 (eIF2) is a central controller of the eukaryotic translational machinery. To sustain the on-going translation activity, eIF2 cycles between its GTP and GDP bound states. However, in response to cellular stresses, the phosphorylation of eIF2 takes place, which acts as an inhibitor of the guanine nucleotide exchange factor eIF2B and switches the translation activity on physiological timescales. The main objective of this work is to investigate the stability of the regulatory system under nominal conditions, parametric fluctuations and structural damages. In this paper, a mathematical model of eIF2 dependent regulatory system is used to identify the stabilityconferring features within the system with the help of direct and indirect methods of Lyapunov stability theory. To investigate the impact of intrinsic fluctuations and structural damages on the stability of regulatory system, the mathematical model has been linearised around feasible equilibrium point and the variation of system poles have been observed. The investigations have revealed that the regulatory model is stable and able to tolerate the intrinsic stressors but becomes unstable when particular complex is targeted to override the undesirable interaction. Our analyses indicate that, the stability is a collective property and damage in the structure of the system changes the stability of the system.

Type: Article
Title: Modelling and Dynamic Behaviour of Eif2 Dependent Regulatory System With Disturbances
Open access status: An open access version is available from UCL Discovery
DOI: 10.1109/TNB.2018.2873027
Publisher version: https://doi.org/10.1109/TNB.2018.2873027
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Protein synthesis, mathematical modelling, structural stability, targeting undesirable interaction, species, elimination
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Electronic and Electrical Eng
URI: https://discovery.ucl.ac.uk/id/eprint/10058854
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