Modeling and Dynamic Behavior of eIF2 Dependent Regulatory System With Disturbances.

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 paper 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 linearized around feasible equilibrium point and the variation of system poles has 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.