The recent development of cryoprobe technology is providing tremendous gains in the inherent sensitivity of solution-state NMR spectrometers. This achievement is of enormous value for NMR studies in the field of structural biology, due to the fundamental role of instrument sensitivity in determining the feasibility of most biomolecular NMR research proposals. Current cryoprobe technology has allowed sensitivity improvements by factors in the range of 2 to 4 to be realized, with the exact gain depending on the conductivity of the sample buffer. In contrast, improvements in sensitivity of conventional NMR probes by as little as 20% have been exceptionally difficult to achieve, and would be considered quite significant. Utilization of a cryoprobe allows sample concentrations to be reduced by factors of 2-4, which greatly facilitates work on samples with low solubility, a tendency to aggregate, or in cases where the sample material is especially difficult and/or costly to obtain. Alternatively, it is possible, by using a cryoprobe, to reduce total data acquisition times by factors of 4 to 16, which is extremely valuable when working on samples of limited stability, when considering projects which require extensive amounts of data to be collected, for allowing for the possibility of performing low-sensitivity experiments in realistic periods of time, and for significantly improving the overall throughput on very costly, ultra-high field NMR spectrometers. In order for structural biologists to continue to tackle increasingly difficult problems, it is vital to exploit whatever technological advances are available. The current proposal requests funds to purchase a triple resonance 5 mm1H-{13C,15N} pulsed field gradient cryoprobe and required accessories for the 800 MHz NMR spectrometer that is housed in the structural biology/NMR facility within the University of Cincinnati College of Medicine. This facility supports a large number of NIH-funded investigators, and acquisition of the cryoprobe will greatly facilitate the existing research projects and will allow new and even more challenging problems to be tackled.
