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.
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