QSB: Understanding Bistability in Complex Enzyme-Driven Reaction Networks

QSB：了解复杂酶驱动反应网络中的双稳定性

• 批准号: 0425459
• 负责人: Martin Feinberg
• 金额: --
• 依托单位: Ohio State University Research Foundation -DO NOT USE
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0425459&HistoricalAwards=false
• 关键词: QSB; Understanding; Bistability; Complex; Enzyme

Feinberg0425459 The main focus of this research is to derive necessary and sufficient conditions for multiple steady states or sustained oscillations in biochemical networks. The Principal Investigator (PI) motivates the research with a simple example of an enzymatically driven reaction that exhibits bistability even in the absence of apparent feedback. The result is derived using chemical reaction network theory previously developed by the PI. A major result from this theory is the Deficiency Zero Theorem that rules out bistability or sustained oscillations in a large class of networks. These results were extended and implemented in the Chemical Reaction Network Toolbox, software written by the PI. The PI has also developed graphical methods for analyzing larger networks. While these methods have proven adequate for analyzing chemical engineering problems, they fail when faced with the complexity of naturally occurring biochemical networks that contain multiple enzymes for the same reaction. Therefore, new theories need to be developed. Chemical reaction network theory mainly gives criteria for ruling out bistability, but when these criteria fail it does not provide conditions for asserting the existence of multiple steady states. The PI proposes to develop such conditions. The PI plans to incorporate into the new theory refined methods for discriminating competing mechanisms for multiple steady states. He also will develop a computer algorithm for drawing and analyzing the Species-Reaction Graph.

Feinberg0425459这项研究的主要重点是推导出生化网络中多个稳态或持续振荡的充分必要条件。主要研究者（PI）用一个简单的酶促反应的例子来激发研究，该反应即使在没有明显反馈的情况下也表现出双稳态。结果是使用PI先前开发的化学反应网络理论得出的。这个理论的一个主要结果是零亏定理，它排除了一大类网络中的双稳性或持续振荡。这些结果在PI编写的化学反应网络工具包中得到了扩展和实现。PI还开发了用于分析大型网络的图形方法。虽然这些方法已被证明足以分析化学工程问题，但当面对包含用于相同反应的多种酶的天然存在的生物化学网络的复杂性时，它们会失败。因此，需要发展新的理论。化学反应网络理论主要给出了排除双稳态的标准，但当这些标准失败时，它并没有提供断言多个稳态存在的条件。PI建议制定此类条件。PI计划将新理论中的精细方法用于区分多个稳态的竞争机制。他还将开发一种计算机算法，用于绘制和分析物种反应图。