Automatic Assembly and Calibration of Models of Enzymatic Reactions Based on Ordinary Differential Equations

Author(s):  
Jure Stojan ◽  
Milan Hodošček ◽  
Dušanka Janežič
Symmetry ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1684
Author(s):  
Alessandro Borri ◽  
Francesco Carravetta ◽  
Pasquale Palumbo

The double phosphorylation/dephosphorylation cycle consists of a symmetric network of biochemical reactions of paramount importance in many intracellular mechanisms. From a network perspective, they consist of four enzymatic reactions interconnected in a specular way. The general approach to model enzymatic reactions in a deterministic fashion is by means of stiff Ordinary Differential Equations (ODEs) that are usually hard to integrate according to biologically meaningful parameter settings. Indeed, the quest for model simplification started more than one century ago with the seminal works by Michaelis and Menten, and their Quasi Steady-State Approximation methods are still matter of investigation nowadays. This work proposes an effective algorithm based on Taylor series methods that manages to overcome the problems arising in the integration of stiff ODEs, without settling for model approximations. The double phosphorylation/dephosphorylation cycle is exploited as a benchmark to validate the methodology from a numerical viewpoint.


Author(s):  
V. F. Edneral ◽  
O. D. Timofeevskaya

Introduction:The method of resonant normal form is based on reducing a system of nonlinear ordinary differential equations to a simpler form, easier to explore. Moreover, for a number of autonomous nonlinear problems, it is possible to obtain explicit formulas which approximate numerical calculations of families of their periodic solutions. Replacing numerical calculations with their precalculated formulas leads to significant savings in computational time. Similar calculations were made earlier, but their accuracy was insufficient, and their complexity was very high.Purpose:Application of the resonant normal form method and a software package developed for these purposes to fourth-order systems in order to increase the calculation speed.Results:It has been shown that with the help of a single algorithm it is possible to study equations of high orders (4th and higher). Comparing the tabulation of the obtained formulas with the numerical solutions of the corresponding equations shows good quantitative agreement. Moreover, the speed of calculation by prepared approximating formulas is orders of magnitude greater than the numerical calculation speed. The obtained approximations can also be successfully applied to unstable solutions. For example, in the Henon — Heyles system, periodic solutions are surrounded by chaotic solutions and, when numerically integrated, the algorithms are often unstable on them.Practical relevance:The developed approach can be used in the simulation of physical and biological systems.


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