MOLECULAR BIOMECHANICS

蛋白质马达利用化学能和电化学能产生 机械力这些力驱动细胞内运动， 多种细胞功能;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 这些分子机器的操作原理是细胞的核心， physiology.最新的进展允许测量力和运动的单一 在微微牛顿和纳米尺度上的大分子，以及结构 研究揭示了蛋白质马达的详细分子结构。 这重新开始了对物理学原理的探索， 大分子系统中的机械化学能量转换。现在可以 制作分子机械化学过程的真实模型， 与观察直接相关，因此可以测试 实验性的 这个项目涉及数学模型的建设，以描述 几类重要的由核苷酸水解驱动的分子马达 和跨膜电动势梯度。 要解决的具体系统是（1）V-ATP酶离子泵;（2） 细菌鞭毛马达;（3）驱动蛋白家族;（4）物理机制 调节运动细胞的板状伪足旋转运动， 控制这些机械化学过程的膜蛋白的定位， 流体环境在分子力化学中的作用 流程.具体来说，由于许多生物分子马达在水溶液中运行， 环境中，并且在尺度上是介观的（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 建议发展中尺度生物流体动力学的计算方法， 浸没的分子机器这些方法还将提供一种手段， 研究渗透力驱动的细胞内水运动。 在每种情况下，建议的方法是开始通过制定随机 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， 数值模拟中的参数已被选择使用最好的 可用的实验数据。将结果与以下机构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 技术将被用来以广泛理解的方式呈现结果。

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.