COMPUTATIONAL STUDIES OF PROTEIN ASSOCIATION IN SOLUTION

这项研究将开发和使用计算 方法来研究原子水平之间的关系， 蛋白质的结构和运动及其生物学功能。 重点将是蛋白质-蛋白质缔合现象， 水介质，处理平衡和动态 关联过程的各个方面。 请注意 对关键的溶剂和电解质的影响， 生理水溶液中的大分子相互作用。 研究的第一部分将侧重于计算 自由能表征相关蛋白质的稳定性 生理溶液条件。 具体来说，均衡 正常人血红蛋白（Hb）与 各种镰状细胞性贫血将从以下发现中阐明： 本研究 研究区域二采用布朗动力学模拟 一种计算蛋白质-蛋白质和蛋白质-配体的方法 扩散缔合速率，以阐明具体的 分子设计的结构原理， 生化反应的扩散相遇阶段。 的 这样制定的方法将成为 计算机辅助化学制剂设计的武器库， 生物医学用途。 将继续研究细胞色素 电子传递系统中的氧化还原伙伴。 知识 对接步骤的动力学将允许结论 关于血红素间电子转移的机理， proteins.

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.