Dynamic Aspects Of Macromolecular Function

大分子功能的动态方面

• 批准号: 6983729
• 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/6983729
• 关键词: atomic force microscopy; calmodulin; chemical kinetics; chemical models; chemical structure function; computer simulation; conformation; macromolecule; mathematical model; molecular dynamics; nanotechnology; nuclear magnetic resonance spectroscopy; photochemistry; physical model; protein folding; thermodynamics

In this reporting period, papers dealing with the following topics appeared in print or have been accepted for publication: (1)Influence of diffusion on the kinetics of excited state association dissociation chemical reactions, (2) Enhancement of association rates by nonspecific binding to DNA and cell membranes (3) Ensemble of transition states for two state protein folding from the eigenvectors of rate matrices and (4) The theory of photon statistics in single molecule Forster resonance energy transfer . The first paper deals with testing the predictions of our general theory or reversible diffusion influenced reactions against the result of many-body computer simulations. In the second paper, we apply this theory to examine the influence of nonspecific binding on the kinetics of binding to receptors on cell membranes and to DNA. In the third paper we propose a new method to analyze kinetic models of protein folding in order to provide insigh into the mechanism. The last and most important paper deals with the theory required to interpret Forster resonance energy transfer experiments on protein folding. In these experiments the number of photons emitted by a donor and an acceptor are monitoried. These contain structural information because the efficiency of energy transfer between tne donor and acceptor depend on the distance between them. Given an arbitrary dynamical scheme we showed how to calculate the probability distribution of the energy transfer obtained for fixed time windows. We have considered the contribution due to shot noise, to conformational dynamics and to translational diffusion in and out of the laser spot. This kind of complete analysis of all contributing factors is essential for the meanigful interpretation of experiments.

在本报告所述期间，有关下列专题的论文已付印或已被接受出版：（1）扩散对激发态缔合解离化学反应动力学的影响，（2）通过与DNA和细胞膜的非特异性结合来提高缔合速率（3）从速率矩阵的本征向量对两态蛋白质折叠的过渡态的Encerning（4）单分子福斯特共振能量转移的光子统计理论。第一篇论文涉及测试我们的一般理论的预测或可逆扩散影响的反应对多体计算机模拟的结果。在第二篇论文中，我们应用这一理论来研究非特异性结合对细胞膜上的受体和DNA结合动力学的影响。在第三篇论文中，我们提出了一种新的方法来分析蛋白质折叠的动力学模型，以提供深入的机制。最后，也是最重要的文件涉及的理论需要解释福斯特共振能量转移实验蛋白质折叠。在这些实验中，由施主和受主发射的光子数被监测。这些包含结构信息，因为供体和受体之间的能量转移效率取决于它们之间的距离。给出了一个任意的动力学方案，我们展示了如何计算固定时间窗口的能量转移的概率分布。我们已经考虑了散粒噪声，构象动力学和平移扩散的激光光斑内外的贡献。这种对所有影响因素的全面分析对于有意义地解释实验至关重要。