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

距离和扭转角信息可以从各种 多维NMR方法，如NOESY和不同的COSY型 实验 然后可以将该几何信息并入 分子力学和分子动力学的约束形式 模拟以产生高分辨率结构。 约束 分子动力学计算导致一种结构， 时间平均固有的NMR导出的约束。 我的研究 努力致力于研究中等规模的相互作用 RNA分子和RNA/蛋白质复合物。 我的重点是 信号识别颗粒的蛋白质-RNA模型系统， 指导蛋白质转运核糖核蛋白系统。 我是 研究一个RNA片段的结构， HIV-1病毒RNA的高度保守部分。 的结构 该保守序列是RNA靶向药物的潜在靶点 设计 计算机图形实验室是不可或缺的， 进行我们富有挑战性的研究 我利用MidasPlus 仔细检查所有NMR衍生的距离，将它们与 所建模的核酸结构的相关距离。 MidasPlus 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。 违反的程度是 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， MidasPlus。 这和监控建筑结构是一样的 在这些计算中发生的变化。 对于我的RNA工作， 大量的模型建造是用布鲁克海文号的碎片完成的 蛋白质数据库晶体结构。 的立体声设施， 计算机图形学实验室是绝对必要的所有 构建更大分子所需的对接。 而且 CGL有助于改进UCSF NMR显示软件 包装，SPARKY，使其成为同类产品中最好的之一。 SPARKY是 与MidasPlus接口，使得特定的模型结构可以 与实验NMR数据直接相关。

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.