Modeling and Dynamic Behavior of eIF2 Dependent Regulatory System With Disturbances

Abstract

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Inbuilt Tendency of the eIF2 Regulatory System to Counteract Uncertainties

“…In order to investigate the ability of the highly engineered eIF2 system to counteract uncertainties, it is necessary to first simplify or linearise the developed nonlinear ODE model. Linear models can be efficiently analysed in the frequency domain which can predict the non-trivial states of the system that are responsible for maintaining its basal activity [17]. The linearisation process is helpful in approximating the higher order nonlinear system by a lower order linear system, through which the local behaviour of nonlinear systems can be estimated around the equilibrium point [37]- [39].…”

“…In order to investigate the origins of robustness within the system with the help of applied control theory, the overall system is converted into a single input single output (SISO) system by eliminating the dynamics of uncharged tRNA and considering it as a control input u [17].…”

“…Investigations have revealed that the eIF2 pathway is robust against uncertainties and can counteract disturbances created by intrinsic stressors [16], [17]. The robustness properties of biomolecular processes against internal and structural disturbances are well known.…”

Semi-Disparate Impact of Kinases GCN2 and PERK in Modulating the Dynamic Control Properties of eIF2 Pathway

“…In this section, a minimization of temporal error functions (ξ 1 and ξ 2 ) is adopted for estimating the unknown rate constants of the model, similar to the one reported by Khan et al in [25]. The minimization of error functions are briefly discussed below.…”

“…In other words, this observation suggests that, the downstream of translation activity due to the activation of kinase GCN2 is different than PERK, and change in the general behavior of the system due to the loss or removal of active kinase GCN2 is not similar to that of loss of activated PERK. Note that, the elimination process has been conducted by using matched DC gain method [25].…”