Acquisition of a state-of-the-art solution phase 4-channel (1H, 19F, 13C, 15N) 800 MHz NMR spectrometer equipped with a triple resonance cryoprobe and a high throughput sample changer, enabling essential fragment-based drug screening capabilities, is proposed. This will enable us to extend essential NMR capabilities at Vanderbilt University, which support a large NIH-funded research portfolio, both in basic biomedical science and translational biomedical research. The major user group consists of six NIH-funded faculty, Profs. Walter Chazin, Doug Kojetin, Jens Meiler, Stephen Fesik, Charles Sanders, and Michael Stone. Many additional NIH- funded minor users also have need for 800 MHz NMR. This instrumentation will satisfy a growing demand for fragment-based drug screening applications, as well as increasing emphasis upon understanding structural aspects of complex binding interactions between biological macromolecules, especially those which rely on the TROSY effect to enhance sensitivity and resolution. It will provide essential 19F capabilities, not presently available. It will provide access to state-of-the-art training in NMR-based structural biology methods for many NIH pre-doctoral and post-doctoral trainees at Vanderbilt University, including trainees from primarily undergraduate institutions serving historically under-represented populations in the STEM and biomedical sciences. Extensive site preparation or renovation will not be necessary because the proposed 800 MHz NMR will be placed in existing space within the Vanderbilt University Biomolecular NMR Facility (VUBNMR), operated by the Vanderbilt Center in Structural Biology (CSB). The VUBNMR Facility is dedicated to studies of biological macromolecules, fragment-based drug discovery, and complex biomolecular binding interactions. It is housed in a dedicated building in the Stevenson Science Center, centrally located on the Vanderbilt campus. It is directed by Prof. Markus Voehler, who has many years of expertise, both in the operation and laboratory support of high field NMR instrumentation. The facility houses a helium liquefier serving NMR cryomagnets. The proposed 800 MHz NMR is anticipated to be used heavily, ~95% of AUT, calculated on a 365 d/yr and 24 h/d basis. Administrative and financial plans for operating and maintaining the 800 MHz NMR and managing laboratory operations are in place.