title: Analysis of protein synthesis dynamic model in eukaryotic cells: Input control.
abstract: This paper presents the analysis of initiation control model of protein synthesis via eukaryotic initiation factor (eIF)-2 unit, introduced by [N.S. Bar, D.R. Morris, Dynamic model of the process of protein synthesis in eukaryoric cells, Bulletin of Mathematical Biology 69 (2007) 361-393, doi:10.1007/s11538-006-9128-2.] and propose methods to control it. Linearization of the model is presented as a measure to simplify the analysis and control application. The properties of the linear model were investigated and compared to the non-linear model using simulations. It was shown that the linear model is (marginally) stable and the states converge to a finite value. Linear optimal control theory can then be applied to the model under the value range where the linearized model is accurate. The effect of the input signals GCN2.tRNA and eIF-2 on the non-linear system was investigated. A few characteristics known from in vitro experiments of the initiation process were proven from a mathematical aspect and some conclusions about the function of the initiation complexes such as eIF2B and the ternary complex were derived. Consistent with published experiments, it was shown that overexpression of eIF-2 increases the concentration of 48S initiation complex and promote initiation rate. A state feedback control was applied in order to manipulate the initiation rate and it was proven that the 48S initiation complex can be driven to a desired value by calculating an input control law using measurement techniques available today. If this strategy can be implemented de facto, then a genuine control on protein synthesis process can be obtained.
authors.affiliation: Norwegian University of Science and Technology, Department of Chemical Engineering, Trondheim NO-7491, Norway. barc@itk.ntnu.no
authors.forename: Nadav S
authors.initials: NS
authors.lastname: Bar
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D005057:Eukaryotic Cells / Q000502:physiology*; D015852:Eukaryotic Initiation Factor-2 / Q000502:physiology; D025461:Feedback, Physiological / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D016014:Linear Models; D008954:Models, Biological; D017711:Nonlinear Dynamics; D014176:Protein Biosynthesis / Q000502:physiology*
chemical_list: D015852:Eukaryotic Initiation Factor-2