COMPUTATIONAL STUDIES OF PROTEIN ASSOCIATION IN SOLUTION

拟议的研究将开发和使用计算机 方法研究原子能级之间的关系 蛋白质的结构和运动及其生物学功能。 重点将放在蛋白质-蛋白质结合现象上 水介质，既涉及平衡又涉及动力学 关联过程的各个方面。我们会把注意力引向 对于关键的溶剂和电解液的影响 生理水溶液中的大分子相互作用。 第一个研究领域将集中在热力学的计算上。 结合蛋白稳定性的自由能表征 生理溶液条件。具体地说，均衡 正常人血红蛋白(Hb)的凝胶常数与 各种镰状细胞性贫血将从以下结果中得到阐明 这项研究。 研究的第二个领域将使用布朗动力学模拟 一种同时计算蛋白质-蛋白质和蛋白质-配体的方法 弥散结合率以阐明特异性 与分子设计有关的结构原理 生化反应的扩散相遇阶段。这个 这样开发的方法将成为 武器库的计算机辅助化学制剂设计 生物医学上的用处。细胞色素方面的工作将继续进行 氧化还原是电子传输系统中的伙伴。了解以下内容 对接步骤的动态将允许得出结论 关于血红素间电子转移的机理 蛋白质。

The proposed study will develop and employ computational methods to investigate the relationship between the atomic-level architecture and motion of proteins and their biological function. The emphasis will be on protein-protein association phenomena in aqueous media, dealing with both equilibrium and dynamical aspects of association processes. Attention will be directed toward the crucial solvent and electrolyte effects which mediate macromolecular interactions in physiological aqueous solutions. Area One of study will focus on calculating the thermodynamical free energies characterizing the stability of associated proteins in physiological solution conditions. Specifically, equilibrium constants for gelation of normal human hemoglobin (Hb) versus various sickle cell anemia will be elucidated from the findings of this study. Area Two of study will employ the Brownian dynamics simulation method to calculate both protein-protein and protein-ligand diffusional association rates in order to elucidate the specific structural principles of molecular design which relate to the diffusional encounter stage of biochemical reactions. The methodology thus developed will become one of the tools in the arsenal of computer-aided design of chemical agents with biomedical usefulness. Work will be continued on cytochrome redox partners in the electron transport system. Knowledge of the dynamics of the docking step will permit conclusions regarding the the mechanism of electron transfer between heme proteins.