COMPACT DOMAINS IN PROTEINS

蛋白质中的紧凑结构域

• 批准号: 2184157
• 负责人: MICHAEL H ZEHFUS
• 金额: $ 9.45万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2184157
• 关键词: artificial intelligence; bacterial proteins; chemical cleavage; chemical stability; circular dichroism; computer program /software; computer simulation; conformation; mathematical model; molecular site; nonwater solvent; nuclear magnetic resonance spectroscopy; nuclease; peptide chemical synthesis; peptide structure; protein folding; protein sequence; protein structure; solutions; synthetic peptide

Structural domains in proteins are regions that are thought to fold autonomously. Previous work by the principal investigator has linked domain structure with physical compactness. Large compact units correspond well to domains while small compact units seem to be folding intermediates or possible folding nucleation sites. Small compact units may also serve as useful entities in protein design. This research will study both experimental and theoretical aspects of the compact domain problem. Experimentally, a series of peptides corresponding to compact and noncompact structures will be obtained using solid phase synthesis or chemical cleavage of the native protein. The peptides' structure will be analyzed using circular dichroism and high resolution two-dimensional NMR. If the structure of the compact peptides closely corresponds to that observed for the peptide within the native protein, while the noncompact peptides have little or no structure, then the compact unit theory will be proven. Theoretical work will focus on discontinuous units containing two different polypeptide chains. Recent advances in computer technology and a new approach to performing calculations should make it possible to analyze for discontinuous compact domains. The examination of discontinuous protein domains should provide new insights into protein structure. Once a good theoretical model for discontinuous compact domains is formulated, it will be experimentally tested using a similar methodology to that used for continuous domains.

蛋白质中的结构域是被认为可以折叠的区域 自主。 首席调查员的先前工作已链接 域结构具有身体紧凑。 大型紧凑型单元对应 远至域，而小紧凑型单元似乎正在折叠中间体 或可能的折叠成核位点。 小紧凑型单元也可能服务 作为蛋白质设计中的有用实体。 这项研究将研究实验和理论方面 紧凑型域问题。 在实验上，一系列相应的肽 将使用固相获得紧凑和不兼容的结构 天然蛋白质的合成或化学裂解。 肽' 结构将使用圆形二科和高分辨率分析 二维NMR。 如果紧密的肽的结构 对应于天然蛋白质中肽的观察到的相对应 虽然非伴随肽几乎没有结构，但紧凑 单位理论将被证明。 理论工作将集中于不连续的单元，其中包含两个不同 多肽链。 计算机技术的最新进展和新的 执行计算方法应该使得分析 不连续的紧凑型域。 不连续蛋白的检查 域应提供有关蛋白质结构的新见解。 曾经是不连续紧凑型域的良好理论模型是 配制，将使用类似的方法对其进行实验测试 它用于连续域。