THEORETICAL STUDIES ON THE DYNAMIC ASPECTS OF MACROMOLECULAR FUNCTION

本文提出了非绝热电子转移速率的分子理论。 发展和它的关系，古典马库斯理论建立。 发现该速率由以下各项的概率密度决定： 能隙，其定义为溶剂化的瞬时变化 电子从施主向受主移动时的能量。 这是 展示了如何从自由能中得到这个概率密度 在供体和受体之间转移不同量的电荷 (as由充电参数指定）。 提出了一种简单的算法 为了计算这些自由能变化（以及由此产生的能隙 概率密度）的计算机模拟，只有三个国家; 反应物、产物和通过转移反应物而形成的"反"产物。 从施主到受主的正单位电荷。 马库斯关系 (i.e.,活化能作为自由能的抛物线函数 反应的变化）是以一种清楚地表明它是 正常区域中的良好近似，即使溶剂响应 是非常非线性的。 这个关系的一个简单概括， 其中活化能由抛物线函数给出， 在正常和倒置区域的不同曲率，提出了。 提出了一种分析核磁共振弛豫实验的新方法 未折叠的蛋白质。 它显示了如何谱密度函数 描述酰胺键矢量的动力学可以在 单独使用N15弛豫参数的特定频率。 实验 关于小蛋白质折叠和未折叠形式的数据被用来 建立这一程序的有效性一个连续模型的 蛋白质中的静电相互作用已被用于分析 一个位置无序的水分子的能量学， 蛋白质表面疏水的空腔，最近已被绑定 实验上使用核磁共振。

A Molecular theory for the rate of nonadiabatic electron transfer was developed and its relation to classical Marcus theory was established. The rate was found to be determined by the probability density of the energy gap, which is defined as the instantaneous change in solvation energy upon moving an electron from the donor to the acceptor. It was shown how this probability density can be obtained from the free energies of transferring varying amounts of charge between the donor and acceptor (as specified by a charging parameter). A simple algorithm was proposed for calculating these free-energy changes (and hence the energy gap probability density) from computer simulations on just three states; the reactant,t he product, and an "anti" product formed by transferring a positive unit charge from the donor to the acceptor. The Marcus relation (i.e., the activation energy as a parabolic function of the free-energy change of reaction) was derived in a way that clearly shows that it is a good approximation in the normal region even when the solvent response is significantly nonlinear. A simple generalization of this relation, in which the activation energy is given by parabolic functions with different curvatures in the normal and inverted regions, was proposed. A novel method has been developed to analyze NMR relaxation experiments on unfolded proteins. It was shown how the spectral density function describing the dynamics of amide bond vectors can be determined at specific frequencies using N15 relaxation parameters alone. Experimental data on the folded and unfolded forms of a small protein was used to establish the validity of this procedure A continuum model of electrostatic interactions in protein has been used to analyze the energetics of a positionally disordered water molecule within an apparently hydrophobic cavity of a protein, as has recently been bound experimentally using NMR.