Project Summary: We propose the acquisition of the first CPMAS cryoprobe for solid-state NMR to be housed in the United States, along with a dedicated 600 MHz NMR spectrometer to support biomolecular research at UC Riverside and the surrounding Southern California region. The increased sensitivity of this instrument will enable transformative research projects supported by NIH funding that include: heterochromatin formation and gene silencing, structural transformations of neurodegenerative disease related proteins (amyloids), membrane protein effectors of pathogen interactions with the host, mechanistic enzymology and chemical structure/dynamics of pyridoxal-5'-phosphate-dependent enzymes, inhibition of β-lactamases, and the mechanics of biopolymers. These problems all share a common need for molecular characterization at the limits of experimental sensitivity. Although well- equipped for solid-state NMR with conventional and dynamic nuclear polarization (DNP) enabled detection, there are currently no facilities within Southern California or North America with the sensitivity of the requested instrumentation for samples that must be maintained at or near room temperature. As such, this equipment will fill a noticeable void in the types of NMR characterization that can be performed both regionally and nationally. The proposed cryoprobe and spectrometer will become part of the University of California at Riverside’s Analytical Chemistry Instrumentation Facility, which serves the campus, local community, and external users from across the country.