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Modelling and dynamic behaviour of eIF2 dependent regulatory system with disturbances

Khan, Mohammad Farhan, Spurgeon, Sarah K., Yan, Xinggang (2018) Modelling and dynamic behaviour of eIF2 dependent regulatory system with disturbances. IEEE Transactions on NanoBioscience, . p. 1. ISSN 1536-1241. E-ISSN 1558-2639. (doi:10.1109/TNB.2018.2873027)

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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 objec-tive 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 stability-conferring 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.

Item Type: Article
DOI/Identification number: 10.1109/TNB.2018.2873027
Uncontrolled keywords: Mathematical model, Proteins, Stress, Stability criteria, Robustness, Biological system modeling
Subjects: T Technology
Divisions: Faculties > Sciences > School of Engineering and Digital Arts
Depositing User: Xinggang Yan
Date Deposited: 03 Oct 2018 13:48 UTC
Last Modified: 04 Oct 2019 23:00 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/69354 (The current URI for this page, for reference purposes)
Yan, Xinggang: https://orcid.org/0000-0003-2217-8398
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