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

距离和扭转角信息可以从不同的 多维核磁共振方法，如NOESY和不同COSY类型 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 模拟以产生高分辨率的结构。克制的人 分子动力学计算导致了一种反映 核磁共振中固有的时间平均派生约束。我的研究 致力于研究中等尺度的相互作用 RNA分子和RNA/蛋白质复合体。我主要强调的是 一种用于信号识别粒子的蛋白质-RNA模型系统 引导蛋白质转位的核糖核蛋白系统。我是 致力于RNA片段的结构阐明，该片段是一种 HIV-1病毒RNA的高度保守的部分。的结构 这个保守的序列是RNA靶向药物的潜在靶点。 设计。计算机图形学实验室是必不可少的 进行我们具有挑战性的研究。我利用MidasPlus来 仔细检查所有核磁共振得出的距离，将它们与 模拟的核酸结构的适当距离。MidasPlus 允许我们直接显示所有由核磁共振派生的距离约束 任何一组相应的坐标。违规的程度是 由颜色编码直接表示。分子动力学模拟 中的动画协议以电影形式观看 MidasPlus。事实证明，这与监视结构 在这些计算中发生的转变。对于我的RNA工作来说，一个很棒的 模型建造的交易是用布鲁克海文的碎片完成的 蛋白质数据库晶体结构。的立体声设备 计算机图形学实验室是所有 建立更大分子所需的对接。此外， CGL有助于改进UCSF核磁共振显示软件 包装，闪闪发光，使其成为同类产品中最好的之一。斯帕奇是 与MidasPlus接口，从而特定的模型结构可以 直接与实验核磁共振数据相联系进行仔细观察。

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.