THEORY OF BIOMOLECULAR DIFFUSION

生物分子扩散理论

• 批准号: 6385478
• 负责人: JAMES ANDREW MCCAMMON
• 金额: $ 26.5万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-06-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6385478
• 关键词: acetylcholinesterase; active sites; biophysics; chemical binding; chemical kinetics; chemical models; computer program /software; computer simulation; conformation; diffusion; enzyme activity; enzyme complex; enzyme substrate; esterase inhibitor; intermolecular interaction; ionic bond; ionic strengths; method development; model design /development; molecular dynamics; protein protein interaction; solutions; thermodynamics

Diffusion governs the rates of many molecular processes of biomedical importance. These processes include the rate of action of enzymes such as acetylcholinesterase, which achieves the high speed necessary for its function in synaptic activity in part by electrostatic guidance of substrate diffusion to its active site. The diffusional encounter of proteins with one another, with lipid bilayers, or with nucleic acids, plays a central role in signal transduction, gene expression, cytoskeletal remodeling, and a host of other processes in cell biology. The broad objectives of this work are to provide new computer simulation tools that will enable the detailed analysis of the role of molecular diffusion in biological processes at the subcellular level, and the application of these tools to selected problems where close contact with experimental work is possible. Specific aims for the next project period include the following. (1) Several improvements will be made in the methods for generating Brownian dynamics trajectories. (2) Methods will be developed to allow for the fluctuation of surface loops on proteins in simulations of protein-protein encounter. (3) Methods will be developed to allow simulations of molecular binding to sites on extended surfaces. (4) Applications will be pursued for several systems for which abundant experimental biophysical data are available. Training of undergraduate, graduate, and postdoctoral students will continue to be a key aspect of this project.

扩散控制着许多具有生物医学重要性的分子过程的速率。这些过程包括酶的作用速率，如乙酰胆碱酯酶，它在突触活动中实现其功能所需的高速，部分是通过静电引导底物扩散到其活性位点。蛋白质相互间、与脂质双分子层或与核酸的扩散相遇在信号转导、基因表达、细胞骨架重塑和细胞生物学中的许多其他过程中起着核心作用。这项工作的主要目标是提供新的计算机模拟工具，以便在亚细胞水平上详细分析分子扩散在生物过程中的作用，并将这些工具应用于可能与实验工作密切接触的选定问题。下一个项目期间的具体目标包括：(1)将对生成布朗动力学轨迹的方法进行若干改进。(2)将开发方法，以允许在蛋白质-蛋白质相遇模拟蛋白质表面环的波动。(3)将开发方法来模拟分子与扩展表面上的位点的结合。(4)将对几个系统进行应用，这些系统有丰富的实验生物物理数据可用。培养本科生、研究生和博士后将继续是这个项目的一个关键方面。