The university of Texas at Austin requests funds for a major upgrade of a 500 MHz NMR spectrometer, to create an instrument equipped with three radiofrequency channels, a high-sensitivity cryoprobe, z-axis pulsed field gradient, and deuterium decoupling. This upgrade will provide NMR capability that is significantly beyond what is currently available at the university, where our most sensitive instrument is currently a 500 MHz conventional-probe instrument. The proposed instrument will enhance the research programs of user groups whose common features are: 1) A need for NMR instrumentation beyond what is currently available at the university; 2) Research directed toward understanding fundamental problems in biochemistry and biophysics; 3) Strong traditions of training graduate and undergraduate students and post-doctoral fellows; 4) NIH- and/or NSFsupported research programs with a significant NMR component. Research in the following areas will be enhanced by the instrument:1. RNA and protein structure (Hoffman)2. Enzyme inhibitor design; engineering of metabolic pathways (Liu)3. Analysis of metabolic pathways using NMR (Appling)4. Synthesis of natural products; synthesis of bioactive targets (Martin)5. Design of nanostructures (Krische)6. Design of novel molecules and ligands (Iverson)7. Metabolic profiling and the characterization of cellular phenotypes (Marcotte). The proposed instrument has the strong endorsement of the university administration, which will provide $65,000 in matching funds. In addition, the university provides laboratory space for housing the instrument, as well as salary and fringe benefits for support personnel.