This proposal requests continued support for the MIT/Harvard Center for Magnetic Resonance (CMR) located at the Francis Bitter Magnet Laboratory, MIT (Grant EB0020261RR-00995). During the coming five-year period we plan significant upgrades of existing equipment, acquisition of new instrumentation, and research initiatives in several new areas. (1) The cluster of NMR and EPR spectrometers currently operating in the facility will continue to be improved with new transmitters, receivers, pulse programmers, computers, etc. (2) We anticipate that the facility will expand with the addition of five instruments: a 900 MHz spectrometer for solution and solid state NMR to be operated as a national facility; a 750 MHz/89 mm magnet and console for the study of amyIoid and membrane proteins; a 800/52 spectrometer for solution NMR; a 460 GHz/700 MHz spectrometer for high field dynamic nuclear polarization experiments; a 140 GHz, 100 watt gyroamplifier for pulsed EPR and DNP experiments (3) In collaboration with industry we purpose the development of a tunable 330 GHz gyrotron oscillator and low temperature MAS probes that can be used to perform DNP experiments with existing 500 MHz/89 mm magnets. This will enable DNP experiments to be transferred to other laboratories. (4) New and continuing areas of interest in the core research program include: (a) high resolution solution NMR spectroscopy of proteins and protein/nucleic acid complexes, (b) structural studies of solids via dipolar recoupling techniques, (c) structural studies of large proteins including enzyme/inhibitor complexes, amyloid, and membrane, (d) CW and pulsed dynamic nuclear polarization, and (e) high frequency CW and pulsed EPR and ENDOR studies of paramagnetic enzymes and enzyme/inhibitor complexes. (5) Significant collaborative research efforts are planned for solution and solid state NMR and high frequency EPR. (6) The service component of the facility remains an important function as is evident by the 19 proposals from outside investigators who have or plan to use the facility frequently. (7) Our plans for training and dissemination include course work in magnetic resonance, seminars, and publication in scholarly journals, and the dispersal of the DNP technology mentioned above.
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