MOLECULAR BIOMECHANICS

蛋白质马达使用化学和电化学能来产生 机械力。这些力驱动细胞内的运动，执行 细胞功能的多样性；例如，制造ATP、泵送离子、穿梭 蛋白质和染色体以及延伸的细胞突起。因此， 这些分子机器的工作原理是细胞的核心 生理学。最近的进步允许测量单个物体的力和运动 皮牛顿和纳米级的大分子，以及结构 研究揭示了蛋白质马达的详细分子结构。 这再次引发了对物理原理的探索 大分子体系中的机械力化学能量转换。现在这是可能的 要制作真实的分子力化学过程模型，可以 与观察结果直接相关，因此可以进行测试 试验性的。 这个项目涉及到建立数学模型来描述 核苷酸水解驱动的几类重要分子马达 和跨膜电动势梯度。 要解决的具体系统是(1)V-ATPase离子泵；(2) 细菌鞭毛运动；(3)运动蛋白家族；(4)物理机制 调节运动细胞的片状脂膜旋转马达和 控制这些机械力化学过程的膜蛋白的定位， (5)流体环境在分子机械力化学中的作用 流程。具体地说，因为许多生物分子马达在水溶液中运行 环境和介观尺度(与水分子相比大，但 仍然足够小，布朗运动是重要的)，奥斯特博士还 建议开发中尺度生物流体动力学的计算方法 沉浸式分子机器。这种方法还将提供一种手段 研究渗透力驱动的细胞内水分运动。 在每种情况下，建议的方法都是从制定随机公式开始 描述分子结构的力学行为的方程。 然后，在可能的情况下，对这些方程进行数学分析，并 到数值模拟，其中的参数是用最好的 可获得的实验数据。结果将与由提供的数据进行比较 实验合作者和同事。计算机动画和其他视觉效果 技术将被用来以一种广泛理解的方式展示结果。

Protein motors use chemical and electrochemical energy to generate mechanical forces. These forces drive intracellular motions that perform a variety of cellular functions; e.g., manufacturing ATP, pumping ions, shuttling proteins and chromosomes and extending cellular protrusions. Thus, the operating principles of these molecular machines are central to cellular physiology. Recent advances permit measuring forces and motions of single macromolecules on the scale of piconewtons and nanometers, and structural studies are revealing the detailed molecular architecture of protein motors. This has renewed the search for the physical principles that underlie mechanochemical energy conversion in macromolecular systems. It is now possible to make realistic models of molecular mechanochemical processes which can be related directly to observations, and which therefore can be tested experimentally. This project involves the construction of mathematical models to describe several important classes of molecular motors driven by nucleotide hydrolysis and transmembrane electromotive gradients. The particular systems to be addressed are (1) the V-ATPase ion pumps; (2)the bacterial flagellar motor; (3) the kinesin family; (4) the physical mechanisms that regulate the lamellipodial rotrusion motor of motile cells and the localization of membrane proteins that control these mechanochemical processes, and (5) the role of the fluid environment in molecular mechanochemical processes. Specifically, because many biomolecular motors operate in an aqueous environment and are mesoscopic in scale (large compared to water molecules but still small enough for Brownian motion to be important), Dr. Oster also proposes to develop computational methods for mesoscale biofluid dynamics with immersed molecular machinery. Such methods will also provide a means of studying intracellular water movements driven by osmotic forces. The proposed approach in each case is to begin by formulating stochastic equations that describe the mechanical behavior of the molecular structures. These equations are then subject to mathematical analyses where possible, and to numerical simulations in which parameters have been chosen using the best available experimental data. Results will be compared to data supplied by experimental collaborators and colleagues. Computer animations and other visual techniques will be used to present results in a broadly understandable manner.