Theoretical Studies On The Dynamic Aspects Of Macromolec

高分子动态方面的理论研究

• 批准号: 7152049
• 负责人: Attila Szabo
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7152049
• 关键词: atomic force microscopy; bioimaging /biomedical imaging; chemical kinetics; chemical models; chemical structure function; conformation; fluorescence spectrometry; macromolecule; mathematical model; molecular /cellular imaging; molecular dynamics; photochemistry; protein folding; quantum chemistry; thermodynamics

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.

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合理应用。此外，它们需要开发新的理论方法来解释它们，以便尽可能地提取最大可能，但仅此而已！)微观信息。这已成为我们最近研究的主要重点。在本报告所述期间，发表的8篇论文涉及以下主题：(1)通过与DNA和细胞膜的非特异性结合提高缔合率(2)从速率矩阵的特征向量集合两态蛋白质折叠的过渡态和(3)单分子Forster共振能量转移中的光子统计理论(4)复杂的扩散激活过程(如蛋白质折叠)的一维反应坐标的存在。(5)在存在相互作用势的情况下扩散影响反应的含时速率系数的新的解析表达式，这将极大地方便实验数据的分析。(6)从单分子力谱(即用原子力显微镜和激光镊子操纵分子的实验)中提取平衡自由能面的方案。(7)两种状态单分子轨迹的信息量(例如，由于膜通道的开启和关闭而开启和关闭离子流)和(8)如何分析荧光单分子发出的时间分辨的光子轨迹，以了解与荧光团猝灭相关的构象变化的本质。前三篇论文在我的上一份报告中作了简要描述。接下来的两个主题涉及化学反应动力学中的基本问题。后三个致力于发展分析单分子作用力和荧光光谱实验所需的理论。