COMPUTATIONAL STUDIES OF PROTEIN ASSOCIATION IN SOLUTION

拟议的研究将开发和采用计算 研究原子水平之间关系的方法 蛋白质的结构和运动及其生物学功能。 重点将放在蛋白质-蛋白质关联现象上 水介质，处理平衡和动态 关联过程的各个方面。 注意力将被引导 朝向介导的关键溶剂和电解质效应 生理水溶液中的大分子相互作用。 研究领域一将集中于计算热力学 表征相关蛋白稳定性的自由能 生理溶液条件。 具体来说，平衡 正常人血红蛋白 (Hb) 的凝胶常数与 各种镰状细胞贫血症将从以下研究结果中得到阐明 这项研究。 研究第二领域将采用布朗动力学模拟 计算蛋白质-蛋白质和蛋白质-配体的方法 扩散关联率，以阐明具体的 分子设计的结构原理，涉及 生化反应的扩散相遇阶段。 的 由此开发的方法将成为 化学制剂计算机辅助设计库 生物医学用途。 细胞色素方面的工作将继续进行 电子传输系统中的氧化还原伙伴。 知识 对接步骤的动态将得出结论 关于血红素之间的电子转移机制 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.