THEORY OF BIOMOLECULAR DIFFUSION

扩散控制着许多具有生物医学重要性的分子过程的速率。 这些过程包括乙酰胆碱酯酶等酶的作用速率，乙酰胆碱酯酶在突触活动中部分通过静电引导底物扩散到其活性位点来实现其功能所必需的高速。 蛋白质彼此、与脂质双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。这项工作的广泛目标是提供新的计算机模拟工具，使详细分析分子扩散在生物过程中的作用，在亚细胞水平上，这些工具的应用，以选定的问题，密切接触的实验工作是可能的。下一个项目期间的具体目标包括以下方面。(1)在生成布朗动力学轨迹的方法上将作一些改进。 (2)将开发方法，以允许在模拟蛋白质-蛋白质相遇的蛋白质表面环的波动。 (3)方法将被开发，以允许模拟分子结合到扩展表面上的网站。 (4)将在已有丰富的实验生物物理数据的几个系统中进行应用。本科生、研究生和博士后的培训将继续是该项目的一个关键方面。

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.