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。我的大部分时间 现在的研究工作致力于研究 中等大小的RNA分子和RNA/蛋白质复合体。我主要强调的是 是建立在蛋白质-RNA模型系统上的信号识别颗粒， 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 L病毒核糖核酸的高度保守部分。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的使用已经 对于执行我们具有挑战性的研究是必不可少的：我利用 MidasPlus通过比较它们来仔细检查所有核磁共振得出的距离 与模拟的核酸结构的适当距离。 MidasPlus允许显示所有由核磁共振得出的距离限制 直接使用任何一组相应的坐标。的程度 违规由颜色编码直接指示。全分子 动力学模拟通常以使用动画的电影形式观看 MidasPlus中的协议。这是一种有效的监视结构 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 模型的制作是用布鲁克海文的碎片完成的 蛋白质数据库晶体结构。这里的立体声设施 CGL实验室对于所有的对接都是绝对必要的 需要建立更大的分子。此外，CGL实验室是 有助于改进核磁共振显示软件包，SPARKY。 Spaky与MidasPlus对接，从而使特定型号 可以直接与实验相联系的结构仔细观察 核磁共振数据。

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. Most of my research efforts are now 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 vira l RNA of HIV-1. The structure of this conserved sequence is a potential target for RNA-targeted drug design. The use of the Computer Graphics Laboratory has been 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 display of all NMR- derived distance restraints directly with any set of the according coordinates. The degree of violation is directly indicated by color coding. All molecular dynamics simulations are usually viewed as a movie using an animation protocol in MidasPlus. This is an efficient way to monitor structural transitions occurring in those calculations. For my RNA work, a great deal of model building was done using fragments from the Brookhaven Protein Databank crystal structures. Here the stereo facilities of the CGL lab are absolutely necessary for all the docking that is needed to build up larger molecules. Furthermore, the CGL lab was instrumental in improving the NMR display software package, SPARKY. SPARKY is interfaced with MidasPlus such that a particular model structure can be scrutinized directly connected with the experimental NMR data.