Dynamic Aspects Of Macromolecular Function

在本报告所述期间，已出版或已接受出版的论文涉及下列主题：(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提高缔合率，(3)从速率矩阵的特征向量合成两态蛋白质折叠的过渡态，以及(4)单分子Forster共振能量转移中的光子统计理论。第一篇论文针对多体计算机模拟的结果来检验我们的一般理论或可逆扩散影响反应的预测。在第二篇论文中，我们应用这一理论来考察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，以期为研究蛋白质折叠的机理提供依据。最后一篇也是最重要的一篇论文涉及解释蛋白质折叠上的Forster共振能量转移实验所需的理论。在这些实验中，对施主和受主发射的光子数量进行了监测。它们包含结构信息，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。在给定任意动力学方案的情况下，我们说明了如何计算在固定时间窗下所获得的能量转移的概率分布。我们考虑了散粒噪声、构象动力学和平移扩散在激光光斑内外的贡献。这种对所有影响因素的完整分析对于有意义地解释实验是必不可少的。

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.