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。 我的大部分 研究工作现在致力于研究的相互作用， 中等大小的RNA分子和RNA/蛋白质复合物。 我主要强调的是 是在信号识别颗粒的蛋白质-RNA模型体系上， 指导蛋白质移位的核糖核蛋白系统。 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 计算机图形学实验室的使用已经 对于执行我们具有挑战性的研究不可或缺：我利用 MidasPlus通过比较它们来仔细检查所有NMR推导的距离 与建模的核酸结构的相关距离。 MidasPlus允许显示所有NMR导出的距离限制 与任何一组相应的坐标直接对应。 程度 违规直接由颜色编码指示。 所有分子 动力学模拟通常被视为使用动画的影片 MidasPlus中的协议。 这是一种有效的方法来监测结构 在这些计算中发生的变化。 对于我的RNA工作， 我们用布鲁克海文号的碎片做了大量的模型 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， 来构建更大的分子。 此外，CGL实验室 有助于改进NMR显示软件包SPARKY。 SPARKY与MidasPlus接口， 结构可以直接与实验联系起来， NMR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.