THEORETICAL STUDIES ON THE DYNAMIC ASPECTS OF MACROMOLECULAR FUNCTION

在本报告所述期间，发表了关于下列项目的论文：（1）热波动势上的反应动力学;（2）经历多态构象动力学的单分子荧光理论;（3）蛋白质折叠的简单模型，说明了理解这一过程所需的大量概念，包括熵垒，过渡态，漏斗和单指数折叠动力学的起源。第一篇论文涉及的重要问题是如何波动的环境，如那些发生在活性位点的酶，影响速率的化学反应。第二篇论文解决的问题，应该如何解释最近和新的荧光实验，而不是散装样品，但对个别分子。第三篇论文介绍了最简单的模型，它抓住了蛋白质折叠的最基本方面，即熵（即构型的数量）和能量随着折叠的发生而减少。这与大多数化学反应相反，在大多数化学反应中，键首先断裂，导致能量增加。有趣的发现是，这个“裸骨”模型能够解释数量惊人的实验趋势，显示这些结果如何遵循最简单的物理假设。

In this reporting period, papers dealing with the following projects appeared in print: (1) Reaction dynamics on a thermally fluctuating potential; (2) Theory of the fluorescence of singlymolecules undergoing multistate conformational dynamics; (3) Asimple model for protein folding that illustrates a large numberof concepts needed to understand this process, including entropic barriers, transition states, funnels and the origin of single exponential folding kinetics. The first paper deals with the important problem of how fluctuations in the environment, such as those that occur in the active site of an enzyme, influence the rate of a chemical reaction. The second paper addresses the problem of how one should interpret recent and novel fluorescence experiments not on bulk samples but on individual molecules. The third paper introduces the simplest model that captures themost fundamental aspect of protein folding, namely that both the entropy (that is the number of configurations) and the energy decrease as folding occurs. This is in contrast to most chemical reactions where bonds are first broken, leading to an increase in energy. The interesting finding is that this "bare bones"model is able to account for a surprising number of experimental trends, showing how such results follow from the simplest physical assumptions.