BROWNIAN DYNAMICS SIMULATIONS OF ACTINS WITH ALDOLASE

肌动蛋白与醛缩酶的布朗动力学模拟

• 批准号: 2024478
• 负责人: KATHRYN A. THOMASSON
• 金额: $ 10.8万
• 依托单位: UNIVERSITY OF NORTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2024478
• 关键词: actins; aldehyde lyase; computer simulation; molecular dynamics

DESCRIPTION: The proposed study will apply theoretical methods to investigate the interactions of G-actin and F-actin with fructose 1,6-bisphosphate aldolase. Brownian dynamics (BD) will simulate the protein-protein associations in aqueous media as influenced by the electrostatics of the proteins; particular attention will be paid to the solvent and electrolyte effects that mediate macromolecular interaction in physiological aqueous solutions. The BD simulations will allow for the study of a large number of BD-docked complexes rather than a single complex, and they will allow for the computation of the mean force versus the docking coordinate so that a free energy curve for the protein docking can be created. The BD method allows for an automated force-guide exhaustive search of docked conformations which would avoid trapping in local energy minima. BD will be able to predict the various kinds of complexes which these proteins can form and their relative stability. The importance of the proposed study relates to the hypothesis that F-actin creates structure in the cell cytoplasm upon which glycolytic enzymes can associate and dissociate dynamically. These dynamic associations may be important to organizing the reactions in the glycolytic pathway. The outcome of this research would be an improved understanding of protein association with actin in solution. It will provide an initial theoretical test for F-actin, thus giving a framework for glycolytic enzymes to function in cells. It will be a first step in understanding the theory behind assembly of structures in the cytoplasmic matrix. Thus, the outcome of this research should have far-reaching implications for cytoplasmic structure and for metabolic regulation.

描述：拟议的研究将应用理论方法， 研究G-肌动蛋白和F-肌动蛋白与果糖的相互作用 1，6-二磷酸醛缩酶。 布朗动力学（BD）将模拟 水介质中蛋白质-蛋白质缔合作用的影响 蛋白质的静电;特别注意将支付给 介导大分子相互作用溶剂和电解质效应 生理水溶液。 BD模拟将允许 研究大量BD对接复合物而不是单个复合物， 它们将允许计算平均力与对接 坐标，使得可以计算蛋白质对接的自由能曲线。 创造 BD方法允许进行自动化的力引导穷举 寻找避免陷入局部能量的对接构象 最小值 BD将能够预测各种复合物， 这些蛋白质可以形成及其相对稳定性。 这项研究的重要性与以下假设有关： 在细胞质中形成糖酵解酶可以 动态地关联和分离。 这些动态关联可以是 对组织糖酵解途径中的反应很重要。 的 这项研究的结果将是对蛋白质的更好理解。 在溶液中与肌动蛋白结合。 它将提供一个初步的理论 测试F-肌动蛋白，从而为糖酵解酶的功能提供框架 在细胞中。 这将是理解背后理论的第一步 细胞质基质中结构的组装。 因此， 研究应该对细胞质结构有深远的影响， 来调节代谢。