THEORETICAL STUDIES ON THE DYNAMIC ASPECTS OF MACROMOLECULAR FUNCTION

在本报告期内，印刷了四篇论文，涉及 (1) 自由能的分解 (2) 理论与模拟 扩散速率影响化学反应（3）的关系 首次通过时间、相关函数和反应速率之间 (4)高强度激光脉冲对荧光的影响 淬火。 现在将依次简要描述这些。 问题 分解配体与蛋白质结合的总自由能 静电范德华等元件最近已成为 引起人们极大兴趣和争议的话题。 我们已经能够展示 通过用以下形式表达自由能微扰展开 平均能量的温度导数，一种天然且有用的 将自由能分解为对应于每个的分量 可以得到哈密顿量中的项。 许多生物过程，例如 作为配体与受体结合，酶-底物复合物形成， 蛋白质 DNA 关联，通常可以描述为扩散影响 反应。 此类反应的速率只能通过分析获得 对于理想化（和不切实际的）模型。 我们开发了一个 处理这些反应的综合理论框架 使用布朗函数获得速率的新颖且有效的方法 动力学计算机模拟。 化学中的一个基本问题 动力学是如何计算单分子反应的速率（例如 作为异构化）从微观动力学。 多年来数 基于第一段的理论提出了替代定义 不可逆过程的时间和平衡波动 由相关函数确定的某些量。 我们曾经 能够在这些看似不同的事物之间找到严格的关系 澄清他们所处环境的方法 等价。 最后，我们已经能够解决有争议的问题 理论上应该如何对待这一长期悬而未决的问题 荧光猝灭实验中的激发脉冲。 我们的工作 表明应如何正确解释此类实验。

In this reporting period, four papers appeared in print dealing with (1) the decomposition of free energies (2) the theory and simulation of the rate of diffusion influenced chemical reaction (3) the relationship between first passage times, correlation functions and reaction rates and (4) the influence of high intensity laser pulses on fluorescence quenching. These will now be briefly described in turn. The problem of decomposing the total free energy of binding of a ligand to a protein into electrostatic Van der Waals etc. components has recently been a subject of great interest and controversy. We have been able to show that by expressing the free energy perturbation expansion in terms of temperature derivatives of the mean energy, a natural and useful decomposition of the free energy into components corresponding to each term in the Hamiltonian can be obtained. Many biological processes such as ligand binding to receptors, enzyme-substrate complex formation, protein DNA association, can often be described as diffusion influenced reactions. The rate of such reactions can only be obtained analytically for idealized (and unrealistic) models. We have developed a comprehensive theoretical framework to treat these reactions which leads to novel and efficient ways of obtaining the rates using Brownian dynamics computer simulations. A fundamental problem in chemical kinetics is how to calculate the rate of unimolecular reactions (such as isomerization) from the microscopic dynamics. Over the years several alternate definitions were proposed based on the theory of first passage times for irreversible processes and on the equilibrium fluctuations of certain quantities as determined by correlation functions. We have been able to find a rigorous relationship between these seemingly different approaches that clarify the circumstances under which they are equivalent. Finally, we have been able to solve the controversial and long outstanding problem of how one should theoretically treat excitation pulses in fluorescence quenching experiments. Our work indicates how such experiments should be correctly interpreted.