Theoretical Studies On The Dynamic Aspects Of Macromolec

在过去的几年里，我们在研究单个大分子的行为方面取得了巨大的进步。这些新的实验需要尖端技术的精密应用。此外，它们需要发展新的理论方法来解释它们，以便提取尽可能多的（但不是更多！）微观信息。这已成为我们最近研究的主要焦点。在本报告所述期间，出版了八篇论文，涉及以下主题：(1)通过非特异性结合DNA和细胞膜提高结合速率(2)从速率矩阵的特征向量得到两态蛋白质折叠的过渡态集合(3)单分子Forster共振能量转移中的光子统计理论(4)蛋白质折叠等复杂扩散激活过程的一维反应坐标的存在。(5)在相互作用势存在的情况下，建立了扩散影响反应时随时间变化的速率系数解析表达式，将极大地促进实验数据的分析。(6)从单分子力谱中提取平衡自由能面（即从原子力显微镜和激光镊子操纵分子的实验中）的协议。(7)两态单分子轨迹（如离子电流因膜通道的开启和关闭而开启和关闭）的信息含量；(8)如何分析荧光单分子发出的时间分辨光子轨迹，以了解与荧光团猝灭相关的构象变化的本质。前三篇论文在我之前的报告中有简要介绍。接下来的两节课讨论化学反应动力学中的基本问题。后三门课致力于发展分析单分子力和荧光光谱实验所需的理论。

Dramatic advances have been made in the last few years in our ability to study the behavior of single macromolecules. These new experiments require sopisticated applications of cutting-edge technologies. Moreover they require the development of new theoretical approaches to interpret them so as to extract the maximum possible but no more!) microscopic information. This has recently become the main focus of our research.In this reporting period, eight papers papers dealing with the following topics appeared in print: (1) Enhancement of association rates by nonspecific binding to DNA and cell membranes (2) Ensemble of transition states for two state protein folding from the eigenvectors of rate matrices and (3) The theory of photon statistics in single molecule Forster resonance energy transfer (4)The existance of a one-dimensional reaction coordinate for complex diffusive activated processes such as protein folding.(5) A new analytic expression for the time dependent rate coefficient of diffusion influenced reactions in the presence of interaction potentials that will greatly facilitate the analysis of experimental data. (6) The protocal of extracting equilibrium free energy surfaces from single molecule force spectroscopy (i.e., from experiments in which molecules are manipulated by atomic force microscopes and laser tweezers). (7) The information content of two state single molecule trajectories (e.g the ionic current turns on and off because of opening and closing of membrane channels) and (8) How to analyze time-resolved photon trajectories emitted by fluorescent single-molecules to learn about the nature of conformational changes associated with the quenching of fluorophores. The first three papers were briefly described in my previous report. The next two deal with fundamental issues in chemical reaction dynamics. The last three are devoted to developping the theory required to analyze single-molecule force and fluorescence spectroscopic experiments.