Progress in FY2012 was made in the following areas: (1) LOW-TEMPERATURE DYNAMIC NUCLEAR POLARIZATION (DNP). DNP is a phenomenon in which irradiation of electron spin transitions with microwaves leads to enhancements of nuclear spin polarizations, and hence enhancements of NMR signals. We have constructed and tested a new cryostat that permits """"""""double-resonance"""""""" DNP measurements (1H and 13C) at temperatures down to 8 K. DNP signal enhancements greater than 20X have been achieved. The design of this cryostat and experimental data, including studies of the dependence of crucial nuclear spin relaxation rate parameters on temperature and dopant concentration, have been published. 2D 13C-13C exchange measurements on amyloid fibrils have been carried out to determine local peptide backbone conformations. These experiments are being written up. We have also constructed a new magic-angle spinning probe with DNP capabilities that operates down to 20 K. DNP enhancements greater than 20X have been achieved, with microwave powers around 30 mW, at 20-25 K and with MAS at 7 kHz. Experimental results are being written up. (2) FREQUENCY-SELECTIVE DIPOLAR RECOUPLING. Dipolar recoupling techniques are techniques for measuring nuclear magnetic dipole-dipole couplings and hence internuclear (or interatomic) distances in solid state NMR. We have applied frequency-selective 13CO-13CO recoupling methods developed in our group to model microcrystaline proteins (SH3 and GB1) and to beta-amyloid fibrils. Along with 15N-15N recoupling measurements, these data place new constraints on backbone conformations in uniformly labeled systems. These techniques have been published in J. Magn. Reson., and we have used these techniques in structural studies of beta-amyloid fibrils. (3) STOCHASTIC DIPOLAR RECOUPLING. We have shown that 13C-13C distances can be measured quantitatively in uniformly 13C-labeled proteins with a new """"""""zero-quantum stochastic dipolar recoupling"""""""" pulse sequence technique. The theory of this method and experimental results on microcrystalline GB1 are described in a paper that is currently in press at the Journal of Chemical Physics. (4) DNP-ENHANCED MRI MICROSCOPY. We have initiated a project to design and construct a magnetic resonance imaging system capable of sub-micron resolution. This MRI system will operate at low temperatures (<10 K) and use dynamic nuclear polarization to enhance proton NMR signals, ultimately enabling signals from voxels with <1 micron dimensions to be detected. A prototype is under construction and will be tested in FY13.

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Thurber, Kent; Tycko, Robert (2016) Low-temperature dynamic nuclear polarization with helium-cooled samples and nitrogen-driven magic-angle spinning. J Magn Reson 264:99-106
Tycko, Robert (2015) On the problem of resonance assignments in solid state NMR of uniformly ¹⁵N,¹³C-labeled proteins. J Magn Reson 253:166-72
Thurber, Kent R; Tycko, Robert (2014) Perturbation of nuclear spin polarizations in solid state NMR of nitroxide-doped samples by magic-angle spinning without microwaves. J Chem Phys 140:184201
Potapov, Alexey; Yau, Wai-Ming; Tycko, Robert (2013) Dynamic nuclear polarization-enhanced 13C NMR spectroscopy of static biological solids. J Magn Reson 231:5-14
Tycko, Robert (2013) NMR at Low and Ultralow Temperatures. Acc Chem Res :
Thurber, Kent R; Tycko, Robert (2012) Theory for cross effect dynamic nuclear polarization under magic-angle spinning in solid state nuclear magnetic resonance: the importance of level crossings. J Chem Phys 137:084508
Hu, Kan-Nian; Qiang, Wei; Bermejo, Guillermo A et al. (2012) Restraints on backbone conformations in solid state NMR studies of uniformly labeled proteins from quantitative amide 15N-15N and carbonyl 13C-13C dipolar recoupling data. J Magn Reson 218:115-27
Hu, Kan-Nian; Qiang, Wei; Tycko, Robert (2011) A general Monte Carlo/simulated annealing algorithm for resonance assignment in NMR of uniformly labeled biopolymers. J Biomol NMR 50:267-76
Thurber, Kent R; Tycko, Robert (2009) Measurement of sample temperatures under magic-angle spinning from the chemical shift and spin-lattice relaxation rate of 79Br in KBr powder. J Magn Reson 196:84-7
Hu, Kan-Nian; Tycko, Robert (2009) Zero-quantum frequency-selective recoupling of homonuclear dipole-dipole interactions in solid state nuclear magnetic resonance. J Chem Phys 131:045101

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