eprintid: 10058854
rev_number: 16
eprint_status: archive
userid: 608
dir: disk0/10/05/88/54
datestamp: 2018-10-19 11:36:50
lastmod: 2020-02-12 16:45:58
status_changed: 2018-10-19 11:36:50
type: article
metadata_visibility: show
creators_name: Khan, MF
creators_name: Spurgeon, SK
creators_name: Yan, XG
title: Modelling and Dynamic Behaviour of Eif2 Dependent Regulatory System With Disturbances
ispublished: pub
divisions: UCL
divisions: A01
divisions: B04
divisions: C05
divisions: F46
keywords: Protein synthesis, mathematical modelling,
structural stability, targeting undesirable interaction, species, elimination
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
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.
date: 2018-10-01
date_type: published
official_url: https://doi.org/10.1109/TNB.2018.2873027
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1593667
doi: 10.1109/TNB.2018.2873027
lyricists_name: Spurgeon, Sarah
lyricists_id: SSPUR40
actors_name: Spurgeon, Sarah
actors_id: SSPUR40
actors_role: owner
full_text_status: public
publication: IEEE Transactions on Nanobioscience
volume: 17
number: 4
pagerange: 518-524
issn: 1536-1241
citation:        Khan, MF;    Spurgeon, SK;    Yan, XG;      (2018)    Modelling and Dynamic Behaviour of Eif2 Dependent Regulatory System With Disturbances.                   IEEE Transactions on Nanobioscience , 17  (4)   pp. 518-524.    10.1109/TNB.2018.2873027 <https://doi.org/10.1109/TNB.2018.2873027>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10058854/1/submitted.pdf