We propose to purchase a 600 MHz Varian Inova Nuclear Magnetic Resonance spectrometer for the Chemistry Department at Stanford University. This instrument will enable researchers to determine high precision structures of macromolecules including proteins, nucleic acids, and protein-protein, protein-ligand, and protein-nucleic complexes. The instrument will directly support the research groups of the P.I. and co-P.I.s (representing approximately 80 researchers), and it is expected that they will be the major users, but will also be available to the Department as a whole (approximately 350 researchers). The instrument will be placed in existing space in the NMR lab in the Chemistry Department, and will be maintained by 2 full-time Ph.D. NMR staffpersons and by 5 graduate assistants. The research proposed specifically identifies the need for a devoted high field NMR instrument for biomolecular structure analysis. Such research includes structural studies of enzymes that synthesize natural product antibiotics, anticancer drugs and the interaction with their target enzymes, a polyketide and derivatives involved in apoptosis, protein-protein and protein-ligand interactions involved in immune response, DNA helices involved in DNA replication and DNA repair, and RNA relating to Hepatitis C virus. All of the P.I.s' research programs are currently supported by NIH and most by NSF as well. Little of this work can be accomplished on current equipment of the Chemistry Department, and all four P.I.s have been forced recently to go elsewhere to carry out needed structural studies, hampering their research. The specific instrumental package we propose to purchase includes the Oxford 14.1 T magnet, as well as supershims, two Fullband RF channels with three total RF channels, waveform generators for each channel, a variable temperature unit, pulsed field gradients, a Sun workstation, and a cryo probe.
