ABSTRACT This proposal requests funds for the purchase of a state-of-the-art Bruker AVANCE NEO 600 MHz high- performance digital NMR spectrometer, which will be housed in the University of Kentucky (UK) PharmNMR Center located in the College of Pharmacy. The requested spectrometer offers capabilities that exceed by far those of the existing NMR instruments currently accessible to the users of this application on campus or anywhere else in the Commonwealth of Kentucky. At UK, there is an urgent need for a high-end, high-field NMR spectrometer for biomedical researchers to be able to: (i) determine structures of small molecules (e.g., synthetic and natural products) in very low amounts as well as determine real-time kinetics; (ii) perform 19F NMR experiments; (iii) establish protein-ligand interactions and/or perform fragment-based drug screening; (iv) determine protein-protein interactions; (v) establish protein dynamics and do relaxation-dispersion experiments; (vi) perform protein structure calculations; (vii) study intrinsically disordered proteins; and (viii) run diffusion ordered spectroscopy (DOSY) experiments. All these capabilities will allow UK researchers to perform cutting- edge work in areas of interest to UK, namely natural product drug discovery and development, infectious diseases and bacterial resistance, cancer, as well as substance use and neurological disorders. The requested instrument will support a widely diverse array of collaborative translational research at UK and is expected to have an immediate and dramatic impact on the NMR-dependent research programs of its NIH-funded researchers.