Basic, simple and extendable kinetic model of protein synthesis

DOI10.3934/MBE.2019329MaRDI QIDQ2045463zbMATH OpenOpenAlexWikidataFDO

Authors Alexander N. Gorban, A. Harel-Bellan, N. Morozova, A. Zinovyev

Publication date 13 August 2021

Published in Mathematical Biosciences and Engineering (Search for Journal in Brave)

Copyright license Creative Commons Attribution 4.0 International

Full work available at URL https://arxiv.org/abs/1204.5941

zbMATH Keywords

kinetic modelinglumpingmodel reductionproteinribosomestranslation

Mathematics Subject Classification ID

Qualitative investigation and simulation of ordinary differential equation models (34C60) Systems biology, networks (92C42) Kinetics in biochemical problems (pharmacokinetics, enzyme kinetics, etc.) (92C45)

Abstract: Protein synthesis is one of the most fundamental biological processes, which consumes a significant amount of cellular resources. Despite existence of multiple mathematical models of translation, varying in the level of mechanistical details, surprisingly, there is no basic and simple chemical kinetic model of this process, derived directly from the detailed kinetic model. One of the reasons for this is that the translation process is characterized by indefinite number of states, thanks to existence of polysomes. We bypass this difficulty by applying a trick consisting in lumping multiple states of translated mRNA into few dynamical variables and by introducing a variable describing the pool of translating ribosomes. The simplest model can be solved analytically under some assumptions. The basic and simple model can be extended, if necessary, to take into account various phenomena such as the interaction between translating ribosomes, limited amount of ribosomal units or regulation of translation by microRNA. The model can be used as a building block (translation module) for more complex models of cellular processes. We demonstrate the utility of the model in two examples. First, we determine the critical parameters of the single protein synthesis for the case when the ribosomal units are abundant. Second, we demonstrate intrinsic bi-stability in the dynamics of the ribosomal protein turnover and predict that a minimal number of ribosomes should pre-exists in a living cell to sustain its protein synthesis machinery, even in the absence of proliferation.

Review text

The paper studies mathematical models of protein synthesis, a core biological process that governs the abundance of proteins in cells. While different mathematical models exist, they study a reduction of this process to a simple chemical kinetic model and its modifications, where unfortunately no references for the original model they consider is given. The lumping to the reduced deterministic model is performed via the so-called ``asymptotology method [\textit{A. N. Gorban}, \textit{O. Radulescu} and \textit{A. Y. Zinovyev}, ``Asymptotology of chemical reaction networks, Chem. Eng. Sci. 65, No. 7, 2310--2324 (2010; \url{doi:10.1016/j.ces.2009.09.005})], and they derive a four-dimensional linear ODE. While the derivation and validity of the reduction is not explained, the reduced model is later expanded. For different extensions they discuss assumptions made and analyse steady states, bistability or other properties. They use explicit calculations to derive steady states, sometimes transient solutions and approximation, and perform simulations in order to compare the models and their biological implications. While the paper is interesting to read, it would have been helpful to further discuss the relationship of their models to other models in the field.

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Cites work

• A MAX-plus model of ribosome dynamics during mRNA translation
• Dynamic model of the process of protein synthesis in eukaryotic cells

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(14)

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• Bifurcations in the interplay of messenger RNA, protein and nonprotein coding RNA
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• Modeling translation in protein synthesis with TASEP: a tutorial and recent developments
• Mathematical modelling of protein secretion across the endoplasmic reticulum
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• A simple protein synthesis model for the PURE system operation
• Modelling co-transcriptional cleavage in the synthesis of yeast pre-rRNA

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