THEORY OF BIOMOLECULAR DIFFUSION

这项工作的长期目标是：（a）发展 双分子定量描述的理论方法 扩散现象，如配体与受体的结合，以及 单分子扩散现象，如运输和某些 分子和分子组装体的构象转变;和（B） 应用这些方法来解释实验数据（例如， 光谱学、动力学、运输），提供机械图，以及 为特定的生物分子设计功能性修饰。 关于（a）项，将利用统计机制提供更多的信息， 真实而准确地描述了 电解质溶液中的分子，并表征 分子反应性的分子内动力学。 此外，理论和 计算研究将继续进行，以提高效率的 布朗动力学计算机模拟，用于研究特定的 模型系统 关于（B），将使用模拟方法来提供 酶催化的精确速率常数，超氧化物歧化酶， 以天然和化学或遗传改变的形式;以及 测定配体与抗体、酶结合的速率 溶菌酶和细胞色素C。 螺旋-卷曲转变的动力学将 确定与结合表面相互作用的多肽， 抗体分子的构象动力学和转运将是 表征了 特定的健康相关性来自于可能的 超氧化物歧化酶在防止再灌注期间的组织损伤中的用途 冠状动脉或肾血管;螺旋诱导在 胰高血糖素和其他激素和肽配体的结合; 在表征的功能细节的理论方法 抗体、酶和其他生物分子;以及 这些方法作为双分子设计工具的实用性。

The long term objectives of this work are (a) the development of theoretical methods for the quantitative description of bimolecular diffusional phenomena such as the binding of ligands to receptors, and of unimolecular diffusional phenomena such as the transport and certain conformational transitions of molecules and molecular assemblies; and (b) the application of these methods to interpret experimental data (e.g., spectroscopic, kinetic, transport), provide mechanistic pictures, and design functional modifications for specific biological molecules. Concerning (a), statistical mechanics will be used to provide more realistic and accurate descriptions of the effective forces between molecules in electrolyte solutions and to characterize the effects of intramolecular dynamics on molecular reactivity. Also, theoretical and computational studies will be pursued to improve the efficiency of the Brownian dynamics computer simulations that are used to study particular model systems. Concerning (b), simulation methods will be used to provide accurate rate constants for catalysis by the enzyme, superoxide dismutase, in both native and chemically or genetically altered forms; and to determine the rate of ligand binding to an antibody, to the enzyme lysozyme, and to cytochrome c. The dynamics of helix-coil transitions will be determined for polypeptides interacting with binding surfaces, and the conformational dynamics and transport of antibody molecules will be characterized. Specific health relatedness arises from the possible utility of superoxide dismutase to prevent tissue damage during reperfusion of coronary or renal blood vessels; the role of helix induction in the binding of glucagon and other hormones and peptide ligands; the utility of the theoretical methods in characterizing details of the function of antibodies, enzymes, and other biological molecules; and the potential utility of these methods as tools for bimolecular design.