9317917 Gorenstein Support is requested for purchase of a 600 MHz NMR console as an upgrade to our Varian VXR 600 NMR spectrometer. Sparcl0 upgrades of computers for a Varian VXR 500 MHz spectrometer and off-line workstation are also requested. These spectrometer upgrades will enhance the NMR capabilities on campus, including the existing Purdue University Biochemical Magnetic Resonance Laboratory (PUBMRL) and an NSF Biological Facilities Center in Biomolecular NMR, Structure and Design. These Centers and the high field spectrometers in the Chemistry Department have sought to provide state-of-the-art high resolution NMR, computer graphics/molecular modeling, and molecular dynamics calculation methodologies to determine the 3D solution structure and dynamics of biomolecules. Pulsed field gradient and triple resonance, 3D and 4D NMR will be made possible by the upgrade. The upgraded console and computers will allow the solution structural determination of much larger proteins, protein drug complexes, and modified oligonucleotide analogs (antisense and ribozymes) than are currently feasible on campus. In a number of collaborative and major user projects, these biomolecules will be synthesized using established synthetic organic methods or through automated DNA or oligopeptide synthesizers. Alternatively, recombinant DNA methodologies will be used to overproduce wild-type and mutant proteins. The various NMR Centers on campus will provide the infrastructure support to determine the 3D structure of the biomolecules via multidimensional NMR methods. Structure and activity of the designed biomolecules will be compared to understand better the structural basis for biological function of these molecules.
