Acquisition of a Fast Shuttle System Apparatus - Funding is requested to obtain a Bruker Biospin Fast Shuttle System (FSS) Apparatus to be installed on an existing 700 MHz NMR spectrometer at the New York Structural Biology Center (NYSBC), a consortium of nine research institutions in New York State. The requested instrumentation is essential to the over-riding purpose of NYSBC and its NIH-funded RM-1 Center for Macromolecular Dynamics by NMR Spectroscopy (CoMD/NMR) to support the specific aims of the NIH-funded research of the major and minor users of the requested instrumentation. The FSS Apparatus is a technological breakthrough that enables for the very first time measurements of spin-lattice relaxation rate constants for 1H, 15N, 13C and other spins in biological macromolecules, including proteins and nucleic acids over the full range of magnetic fields from 100 µT to 16.4 T (termed R1 relaxation dispersion or relaxometry) The FSS Apparatus consists of a fast shuttle system, a magnetic tunnel inserted into the bore of the NMR dewar, and an external electromagnet field cycling coil (FCC) mounted on top of the NMR magnet dewar. The key part of the FSS Apparatus is the magnetic tunnel, which maintains the minimum field in the bore of the magnet >1 T in order to prevent extremely large increases in R1 during transfer from high field (in the superconducting coil) to low field (in the FCC) and back. Consequently, sensitivity is dramatically increased, relaxation effects during shuttling of the sample are minimized, and lower magnetic fields can be accessed, compared to existing shuttle systems lacking a magnetic tunnel or FCC (relying only on the fringe field of the superconducting coil). The FCC is designed to operate in the range 100 µT to 0.8 T, while the fringe field of the spectrometer is used to measure relaxation rates at fields > 0.8 T. Both theoretical calculations and preliminary measurements of 15N and 13C R1 relaxation dispersion demonstrate that conformational dynamics of biological macromolecules can be characterized in unprecedented detail using the FSS, compared with high-field measurements (>10 T) or relaxometry using only the fringe field (>0.5 T). The requested FSS Apparatus will be the third one in the world and first in the United States; thus, a key goal of CoMD/NMR is to make this groundbreaking technology available to the major and minor users, but also to the national research community. The research conducted using this transformative technology ranges from fundamental studies of structure/dynamics/function of biomolecules, to elucidation of mechanisms of pathogenesis, to discovery of novel lead compounds, and to pharmaceutical applications.
