THEORETICAL STUDIES ON THE DYNAMIC ASPECTS OF MACROMOLECULAR FUNCTION

在本报告所述期间，印刷了四份文件，涉及(1) 自由能分解(2)自由能分解的理论与模拟 扩散速度影响化学反应(3)关系 首次通过时间、相关函数和反应速率之间的关系 以及(4)高强度激光脉冲对荧光的影响 淬火。现在将依次对这些内容进行简要描述。问题 分解配基与蛋白质结合的总自由能 成静电的范德华等组件最近已成为 引起极大兴趣和争议的话题。我们已经能够证明 通过将自由能微扰展开式表示为 温度导数的平均能量，一个自然而有用的 将自由能分解成与每个自由能对应的分量 可以得到哈密顿量中的项。许多生物过程，如 作为配体与受体结合，酶-底物复合体形成， 蛋白质DNA结合，通常可以被描述为扩散影响 反应。这种反应的速度只能通过分析来获得。 用于理想化的(和不现实的)模型。我们已经开发出一种 全面的理论框架来处理这些导致 利用布朗函数求取利率的新的有效方法 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(如 作为异构化)从微观动力学。多年来，有几个 另一种定义是基于第一次通过理论提出的 不可逆过程的时间与平衡涨落 由相关函数确定的某些量。我们一直在 能够在这些看似不同的人之间找到一种严格的关系 澄清它们所处的情况的方法 等价物。最后，我们已经能够解决有争议的和 理论上应该如何对待的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 指示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.