THEORETICAL STUDIES ON THE DYNAMIC ASPECTS OF MACROMOLECULAR FUNCTION

大分子功能动力学方面的理论研究

• 批准号: 6161932
• 负责人: A SZABO
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6161932
• 关键词: chemical association; chemical kinetics; chemical models; chemical structure function; computer simulation; conformation; diffusion; ligands; macromolecule; mathematical model; molecular dynamics; nuclear magnetic resonance spectroscopy; photochemistry; proteins; thermodynamics

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.

在此报告期间，出现了四篇论文。 自由能的分解（2） 扩散速率影响化学反应（3）关系 在第一次通过时间，相关函数和反应速率 （4）高强度激光脉冲对荧光的影响 淬火。 这些现在将依次简要描述。 问题 分解配体与蛋白质结合的总自由能 进入静电范德华等。组件最近是一个 引起极大的兴趣和争议的主题。 我们已经能够展示 通过以 平均能量的温度衍生物，一种天然有用的 将自由能分解为对应于每个的组件 可以获得哈密顿量的术语。 许多生物过程 作为配体与受体的结合，酶 - 基底复合物的形成， 蛋白DNA关联通常可以描述为受扩散影响 反应。 这种反应的速率只能在分析上获得 用于理想化（和不现实的）模型。 我们已经开发了 全面的理论框架来治疗这些反应 使用新颖有效的方式使用布朗人获取利率 动态计算机模拟。 化学的基本问题 动力学是如何计算单分子反应的速率（这样 从显微动力学开始的异构化）。 多年来 根据第一段理论提出了替代定义 不可逆过程和平衡波动的时间 由相关函数确定的某些数量。 我们去过 能够在这些看似不同的之间找到严格的关系 阐明他们处于情况的方法 相等的。 最后，我们能够解决争议和 理论上应该如何对待的长期出现的问题 荧光淬灭实验中的激发脉冲。 我们的工作 指示如何正确解释此类实验。