It is proposed to expand the capability to perform modern multi-nuclear solid state NMR experiments at the University of Washington by replacing an obsolete, home-built single r.f. channel 500 MHz NMR console with a commercial triple channel solid state NMR console. The number of groups involved in performing solid state NMR experiments independently or collaboratively with Gary Drobny's research group has increased in recent years. The research group of Professor Gabriele Varani (Chemistry/Biochemistry) uses both solid state NMR and solution NMR to investigate the nature of internal motions in nucleic acids and the role that these motions might play in nucleic acid-protein recognition. Professor Patrick Stayton (Bioengineering), and Professor Gary Drobny (Chemistry) use solid state NMR to study the structure and dynamics of proteins at biomaterial interfaces, and Rachel Klevit (Biochemistry) uses solid state to study the structure of microcrystalline proteins that are intractable to solution NMR methods. Gary Drobny also uses solid state NMR to study peptide structure on biomaterial surfaces. To accommodate these research programs, the availability of solid state NMR instrumentation at UW needs to be expanded. We propose to do this in a cost-effective way by augmenting the capabilities of the Bruker DMX-750 spectrometer with a triple resonance MAS probe. Not all solid state NMR experiments need to be performed at 17.6 T, so to accommodate the majority of groups wanting to do solid state NMR we propose to replace a single channel homebuilt 500 MHz. console with a commercial triple channel NMR console.
Knowledge of the structure and dynamics of bio-molecules is fundamental to understanding their function. The Major-Users of the Solid State NMR Instrumentation requested in this application investigate: 1) the nature of protein-RNA interactions with relevance to the design of drugs that target HIV viral RNA;2) the nature of protein-biomaterial surface interactions with a view to derive design principles for biosensors, and coatings for medical implants;and 3) the structure of heat shock proteins, that bind and sequester unfolded proteins.
