Universally valid reduction of multiscale stochastic biochemical systems using simple non-elementary propensities.

Biochemical systems consist of numerous elementary reactions governed by the law of mass action. However, experimentally characterizing all the elementary reactions is nearly impossible. Thus, over a century, their deterministic models that typically contain rapid reversible bindings have been simpl...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yun Min Song, Hyukpyo Hong, Jae Kyoung Kim
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6bae837c4e054f7a89f24fe2c3bf1861
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6bae837c4e054f7a89f24fe2c3bf1861
record_format	dspace
spelling	oai:doaj.org-article:6bae837c4e054f7a89f24fe2c3bf18612021-12-02T19:57:29ZUniversally valid reduction of multiscale stochastic biochemical systems using simple non-elementary propensities.1553-734X1553-735810.1371/journal.pcbi.1008952https://doaj.org/article/6bae837c4e054f7a89f24fe2c3bf18612021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1008952https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Biochemical systems consist of numerous elementary reactions governed by the law of mass action. However, experimentally characterizing all the elementary reactions is nearly impossible. Thus, over a century, their deterministic models that typically contain rapid reversible bindings have been simplified with non-elementary reaction functions (e.g., Michaelis-Menten and Morrison equations). Although the non-elementary reaction functions are derived by applying the quasi-steady-state approximation (QSSA) to deterministic systems, they have also been widely used to derive propensities for stochastic simulations due to computational efficiency and simplicity. However, the validity condition for this heuristic approach has not been identified even for the reversible binding between molecules, such as protein-DNA, enzyme-substrate, and receptor-ligand, which is the basis for living cells. Here, we find that the non-elementary propensities based on the deterministic total QSSA can accurately capture the stochastic dynamics of the reversible binding in general. However, serious errors occur when reactant molecules with similar levels tightly bind, unlike deterministic systems. In that case, the non-elementary propensities distort the stochastic dynamics of a bistable switch in the cell cycle and an oscillator in the circadian clock. Accordingly, we derive alternative non-elementary propensities with the stochastic low-state QSSA, developed in this study. This provides a universally valid framework for simplifying multiscale stochastic biochemical systems with rapid reversible bindings, critical for efficient stochastic simulations of cell signaling and gene regulation. To facilitate the framework, we provide a user-friendly open-source computational package, ASSISTER, that automatically performs the present framework.Yun Min SongHyukpyo HongJae Kyoung KimPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 10, p e1008952 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Yun Min Song Hyukpyo Hong Jae Kyoung Kim Universally valid reduction of multiscale stochastic biochemical systems using simple non-elementary propensities.
description	Biochemical systems consist of numerous elementary reactions governed by the law of mass action. However, experimentally characterizing all the elementary reactions is nearly impossible. Thus, over a century, their deterministic models that typically contain rapid reversible bindings have been simplified with non-elementary reaction functions (e.g., Michaelis-Menten and Morrison equations). Although the non-elementary reaction functions are derived by applying the quasi-steady-state approximation (QSSA) to deterministic systems, they have also been widely used to derive propensities for stochastic simulations due to computational efficiency and simplicity. However, the validity condition for this heuristic approach has not been identified even for the reversible binding between molecules, such as protein-DNA, enzyme-substrate, and receptor-ligand, which is the basis for living cells. Here, we find that the non-elementary propensities based on the deterministic total QSSA can accurately capture the stochastic dynamics of the reversible binding in general. However, serious errors occur when reactant molecules with similar levels tightly bind, unlike deterministic systems. In that case, the non-elementary propensities distort the stochastic dynamics of a bistable switch in the cell cycle and an oscillator in the circadian clock. Accordingly, we derive alternative non-elementary propensities with the stochastic low-state QSSA, developed in this study. This provides a universally valid framework for simplifying multiscale stochastic biochemical systems with rapid reversible bindings, critical for efficient stochastic simulations of cell signaling and gene regulation. To facilitate the framework, we provide a user-friendly open-source computational package, ASSISTER, that automatically performs the present framework.
format	article
author	Yun Min Song Hyukpyo Hong Jae Kyoung Kim
author_facet	Yun Min Song Hyukpyo Hong Jae Kyoung Kim
author_sort	Yun Min Song
title	Universally valid reduction of multiscale stochastic biochemical systems using simple non-elementary propensities.
title_short	Universally valid reduction of multiscale stochastic biochemical systems using simple non-elementary propensities.
title_full	Universally valid reduction of multiscale stochastic biochemical systems using simple non-elementary propensities.
title_fullStr	Universally valid reduction of multiscale stochastic biochemical systems using simple non-elementary propensities.
title_full_unstemmed	Universally valid reduction of multiscale stochastic biochemical systems using simple non-elementary propensities.
title_sort	universally valid reduction of multiscale stochastic biochemical systems using simple non-elementary propensities.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/6bae837c4e054f7a89f24fe2c3bf1861
work_keys_str_mv	AT yunminsong universallyvalidreductionofmultiscalestochasticbiochemicalsystemsusingsimplenonelementarypropensities AT hyukpyohong universallyvalidreductionofmultiscalestochasticbiochemicalsystemsusingsimplenonelementarypropensities AT jaekyoungkim universallyvalidreductionofmultiscalestochasticbiochemicalsystemsusingsimplenonelementarypropensities
_version_	1718375844563386368

Universally valid reduction of multiscale stochastic biochemical systems using simple non-elementary propensities.

Ejemplares similares