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自顶向下到自底向上:细胞氧化还原网络的计算建模方法。

From top-down to bottom-up: computational modeling approaches for cellular redoxin networks.

机构信息

School of Life Sciences, University of Kwa-Zulu Natal, Scottsville, South Africa.

出版信息

Antioxid Redox Signal. 2013 Jun 1;18(16):2075-86. doi: 10.1089/ars.2012.4771. Epub 2013 Feb 4.

DOI:10.1089/ars.2012.4771
PMID:23249367
Abstract

SIGNIFICANCE

Thioredoxin, glutaredoxin, and peroxiredoxin systems play critical roles in a large number of redox-sensitive cellular processes. These systems are linked to each other by coupled redox cycles and common reaction intermediates into a larger network. Given the scale and connectivity of this network, computational approaches are required to analyze its dynamics and organization.

RECENT ADVANCES

Theoretical advances, as well as new redox proteomic methods, have led to the development of both top-down and bottom-up systems biology approaches to analyze the these systems and the network as a whole. Top-down approaches have been based on modifications to the Nernst equation or on graph theoretical approaches, while bottom-up approaches have been based on kinetic or stoichiometric modeling techniques.

CRITICAL ISSUES

This review will consider the rationale behind these approaches and focus on their advantages and limitations. Further, the review will discuss modeling standards to ensure model accuracy and availability.

FUTURE DIRECTIONS

Top-down and bottom-up approaches have distinct strengths and limitations in describing cellular redoxin networks. The availability of methods to overcome these limitations, together with the adoption of common modeling standards, is expected to increase the pace of model-led discovery within the redox biology field.

摘要

意义

硫氧还蛋白、谷氧还蛋白和过氧化物酶系统在大量的氧化还原敏感细胞过程中发挥关键作用。这些系统通过偶联的氧化还原循环和共同的反应中间体相互联系,形成一个更大的网络。鉴于这个网络的规模和连通性,需要计算方法来分析其动态和组织。

最新进展

理论上的进展以及新的氧化还原蛋白质组学方法,导致了自上而下和自下而上的系统生物学方法的发展,以分析这些系统和整个网络。自上而下的方法基于对能斯特方程的修改或图论方法,而下自下而上的方法则基于动力学或计量建模技术。

关键问题

这篇综述将考虑这些方法的基本原理,并重点讨论它们的优点和局限性。此外,该综述将讨论建模标准,以确保模型的准确性和可用性。

未来方向

自上而下和自下而上的方法在描述细胞氧化还原网络方面具有明显的优势和局限性。克服这些局限性的方法的可用性,以及共同建模标准的采用,有望加快氧化还原生物学领域的模型主导发现的步伐。

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