THEORETICAL STUDIES ON THE DYNAMIC ASPECTS OF MACROMOLECULAR FUNCTION

在本报告所述期间，印发了四份文件，涉及（1） 自由能分解;（2） 扩散速率影响化学反应（3） 在第一次通过时间、相关函数和反应速率之间 （4）强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 静电货车范德瓦耳斯等部件的制造方法， 这是一个非常有趣和有争议的话题。 我们已经能够证明 通过将自由能微扰展开表示为 平均能量的温度导数，一个自然的和有用的 将自由能分解成对应于每个 可以得到哈密顿量中的项。 许多生物过程，如 如配体与受体的结合，酶-底物复合物的形成， 蛋白质与DNA的结合，通常可以被描述为扩散影响 反应. 这类反应的速率只能用解析法求得 理想化（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反应， 到新颖和有效的方法获得率使用布朗 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， 基于首次通过理论，提出了替代定义 时间的不可逆过程和平衡波动的 由相关函数确定的某些量。 我们一直 能够找到这些看似不同的 这些方法澄清了它们在何种情况下 相当于 最后，我们已经能够解决有争议的， 一个长期悬而未决的问题，一个人应该如何在理论上对待 荧光猝灭实验中的激发脉冲。 我们的工作 指出了如何正确解释这些实验。

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.