ELUCIDATION OF SOLUTION STRUCTURES OF RNA & RNA PROTEIN COMPLEXES: HIV

RNA 溶液结构的阐明

• 批准号: 6220318
• 负责人: ULI SCHMITZ
• 金额: $ 0.6万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6220318
• 关键词: aging; biological products; biomedical resource; communication behavior

Distance and torsion angle information can be gleaned from various multidimensional NMR methods, such as NOESY and different COSY-type experiments. This geometrical information can then be incorporated in form of restraints for molecular mechanics and molecular dynamics simulations to yield high resolution structures. The restrained molecular dynamics calculations lead to a structure reflecting the time-average inherent in the NMR derived constraints. My research efforts are dedicated to the study of the interaction of medium size RNA molecules and RNA/protein complexes. My main emphasis is on a protein-RNA model system for the signal recognition particle, a ribonucleoprotein system that direct protein translocation. I am working on the structure elucidation of an RNA fragment which is a highly conserved part of the viral RNA of HIV-1. The structure of this conserved sequence is a potential target for RNA-targeted drug design. The Computer Graphics Laboratory is indispensable for performing our challenging research. I utilize MidasPlus to scrutinize all NMR-derived distances by comparing them with the pertinent distances of the modeled nucleic acid structures. MidasPlus allows us to display all NMR-derived distance restraints directly with any set of the according coordinates. The degree of violation is directly indicated by color coding. Molecular dynamics simulations are usually viewed as a movie using an animation protocol in MidasPlus. This turns out to be the same way to monitor structural transitions occurring in those calculations. For my RNA work, a great deal of model building is done using fragments from the Brookhaven Protein Databank crystal structures. The stereo facilities of the Computer Graphics Laboratory are absolutely necessary for all the docking that is needed to build up larger molecules. Furthermore, the CGL was instrumental in improving the UCSF NMR display software package, SPARKY, making it one of the finest of its kind. SPARKY is interfaced with MidasPlus such that a particular model structure can be scrutinized directly connected with the experimental NMR data.

距离和扭转角度信息可以从各种收集 多维 NMR 方法，例如 NOESY 和不同的 COSY 型 实验。 然后可以将该几何信息合并到 分子力学和分子动力学的约束形式 模拟产生高分辨率结构。 内敛的 分子动力学计算得出的结构反映了 NMR 导出的约束中固有的时间平均。 我的研究 致力于研究中等尺寸的相互作用 RNA 分子和 RNA/蛋白质复合物。 我的主要重点是 信号识别颗粒的蛋白质-RNA模型系统 指导蛋白质易位的核糖核蛋白系统。 我是 致力于RNA片段的结构阐明 HIV-1病毒RNA的高度保守部分。 的结构 这个保守序列是 RNA 靶向药物的潜在靶点 设计。 计算机图形学实验室是不可或缺的 进行我们具有挑战性的研究。 我利用 MidasPlus 来 通过将所有 NMR 得出的距离与 建模核酸结构的相关距离。 迈达斯Plus 允许我们直接显示所有 NMR 导出的距离限制 任何一组相应的坐标。 违规程度为 直接用颜色编码表示。 分子动力学模拟 通常被视为使用动画协议的电影 迈达斯加。 事实证明，这与监测结构的方法相同。 这些计算中发生的转变。 对于我的 RNA 工作来说，一个伟大的 模型构建的交易是使用布鲁克海文的碎片完成的 蛋白质数据库晶体结构。 音响设施 计算机图形学实验室对于所有的人来说都是绝对必要的 构建更大分子所需的对接。 此外， CGL 在改进 UCSF NMR 显示软件方面发挥了重要作用 包装，SPARKY，使其成为同类中最好的包装之一。 火花是 与 MidasPlus 接口，以便特定的模型结构可以 直接与实验 NMR 数据相关联进行检查。