Progress in FY2011 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. Preliminary studies indicate DNP signal enhancements up to 20X. 2D 13C-13C exchange measurements on amyloid fibrils have been carried out to determine local peptide backbone conformations. We have also constructed a new magic-angle spinning probe with DNP capabilities that operates down to 20 K. Testing of this probe is in progress. (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. (3) SEMI-AUTOMATED RESONANCE ASSIGNMENTS IN SOLID STATE NMR. We have developed a new computational protocol for sequential assignment of chemical shifts in multidimensional solid state NMR spectra of uniformly 15N,13C-labeled proteins. This method uses a novel Monte Carlo/simulated annealing (MC/SA) approach to assign crosspeak signals to individual residues in a manner that maximizes a scoring function, which favors sequential matches of relevant chemical shifts, disfavors mismatches, and favors contiguous stretches of residues with assigned signals. This computational approach replaces manual assignment procedures that are highly subjective, error-prone, and incomplete in their analysis of the information content of the NMR data. In FY2011, we have developed a very general version of the MC/SA program that is applicable to virtually any combination of multidimensional chemical shift correlation data in solid state NMR.

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Tycko, Robert (2018) Indirect detection in solid state NMR: An illustrious history and a bright future. J Magn Reson 288:122-123
Thurber, Kent R; Le, Thanh-Ngoc; Changcoco, Victor et al. (2018) Verdazyl-ribose: A new radical for solid-state dynamic nuclear polarization at high magnetic field. J Magn Reson 289:122-131
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 ¹?N,¹³C-labeled proteins. J Magn Reson 253:166-72
Potapov, Alexey; Yau, Wai-Ming; Ghirlando, Rodolfo et al. (2015) Successive Stages of Amyloid-? Self-Assembly Characterized by Solid-State Nuclear Magnetic Resonance with Dynamic Nuclear Polarization. J Am Chem Soc 137:8294-307
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
Tycko, Robert (2014) Remote sensing of sample temperatures in nuclear magnetic resonance using photoluminescence of semiconductor quantum dots. J Magn Reson 244:64-7
Yau, Wai-Ming; Thurber, Kent R; Tycko, Robert (2014) Synthesis and evaluation of nitroxide-based oligoradicals for low-temperature dynamic nuclear polarization in solid state NMR. J Magn Reson 244:98-106
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 46:1923-32

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