Facing and Overcoming Sensitivity Challenges in Biomolecular NMR Spectroscopy.

In the Spring of 2013, NMR spectroscopists convened at the Weizmann Institute in Israel to brainstorm on approaches to improve the sensitivity of NMR experiments, particularly when applied in biomolecular settings. This multi-author interdisciplinary Review presents a state-of-the-art description of the primary approaches that were considered. Topics discussed included the future of ultrahigh-field NMR systems, emerging NMR detection technologies, new approaches to nuclear hyperpolarization, and progress in sample preparation. All of these are orthogonal efforts, whose gains could multiply and thereby enhance the sensitivity of solid- and liquid-state experiments. While substantial advances have been made in all these areas, numerous challenges remain in the quest of endowing NMR spectroscopy with the sensitivity that has characterized forms of spectroscopies based on electrical or optical measurements. These challenges, and the ways by which scientists and engineers are striving to solve them, are also addressed.

[1]  Saikat Saha,et al.  Design, construction, and validation of a 1-mm triple-resonance high-temperature-superconducting probe for NMR. , 2006, Journal of magnetic resonance.

[2]  M. Bardet,et al.  Rapid natural-abundance 2D 13C-13C correlation spectroscopy using dynamic nuclear polarization enhanced solid-state NMR and matrix-free sample preparation. , 2012, Angewandte Chemie.

[3]  G. De Paëpe,et al.  Matrix-free dynamic nuclear polarization enables solid-state NMR 13C-13C correlation spectroscopy of proteins at natural isotopic abundance. , 2013, Chemical communications.

[4]  V. Denysenkov,et al.  Liquid state DNP of water at 9.2 T: an experimental access to saturation. , 2013, Physical chemistry chemical physics : PCCP.

[5]  Speeding up sequence specific assignment of IDPs , 2012, Journal of biomolecular NMR.

[6]  C. Rienstra,et al.  GFT projection NMR spectroscopy for proteins in the solid state , 2010, Journal of biomolecular NMR.

[7]  Christian Griesinger,et al.  (1)H and (13)C dynamic nuclear polarization in aqueous solution with a two-field (0.35 T/14 T) shuttle DNP spectrometer. , 2009, Journal of the American Chemical Society.

[8]  A. Pines,et al.  Proton‐Enhanced Nuclear Induction Spectroscopy. A Method for High Resolution NMR of Dilute Spins in Solids , 1972 .

[9]  Lucio Frydman,et al.  Progress in hyperpolarized ultrafast 2D NMR spectroscopy. , 2008, Chemphyschem : a European journal of chemical physics and physical chemistry.

[10]  Bowers,et al.  Transformation of symmetrization order to nuclear-spin magnetization by chemical reaction and nuclear magnetic resonance. , 1986, Physical review letters.

[11]  S. Keith FACTORS INFLUENCING THE SURVIVAL OF BACTERIA AT TEMPERATURES IN THE VICINITY OF THE FREEZING POINT OF WATER. , 1913, Science.

[12]  Deniz Sezer Computation of DNP coupling factors of a nitroxide radical in toluene: seamless combination of MD simulations and analytical calculations. , 2013, Physical chemistry chemical physics : PCCP.

[13]  Peder E. Z. Larson,et al.  Multiband excitation pulses for hyperpolarized 13C dynamic chemical-shift imaging. , 2008, Journal of magnetic resonance.

[14]  Elizabeth C. Theil,et al.  NMR reveals pathway for ferric mineral precursors to the central cavity of ferritin , 2009, Proceedings of the National Academy of Sciences.

[15]  Peter Hoefer,et al.  Shuttle DNP spectrometer with a two-center magnet. , 2010, Physical chemistry chemical physics : PCCP.

[16]  John Kurhanewicz,et al.  Analysis of cancer metabolism by imaging hyperpolarized nuclei: prospects for translation to clinical research. , 2011, Neoplasia.

[17]  A. Kentgens,et al.  A High-Conversion-Factor, Double-Resonance Structure for High-Field Dynamic Nuclear Polarization , 2009 .

[18]  Eduard Y Chekmenev,et al.  Hyperpolarized (1)H NMR employing low gamma nucleus for spin polarization storage. , 2009, Journal of the American Chemical Society.

[19]  Robert G Griffin,et al.  Dynamic nuclear polarization at high magnetic fields. , 2008, The Journal of chemical physics.

[20]  M. Rodak,et al.  TEMPERATURE OF SPIN-SPIN INTERACTIONS IN ELECTRON SPIN RESONANCE , 1972 .

[21]  L. Kay,et al.  Isotope labeling strategies for the study of high-molecular-weight proteins by solution NMR spectroscopy , 2006, Nature Protocols.

[22]  Richard Eisenberg,et al.  Para hydrogen induced polarization in hydrogenation reactions , 1987 .

[23]  Patrick Walsh,et al.  Probing dynamic conformations of the high-molecular-weight αB-crystallin heat shock protein ensemble by NMR spectroscopy. , 2012, Journal of the American Chemical Society.

[24]  S. Duckett,et al.  Applications of the parahydrogen phenomenon: A chemical perspective , 1999 .

[25]  Kurt W Zilm,et al.  Preparation of protein nanocrystals and their characterization by solid state NMR. , 2003, Journal of magnetic resonance.

[26]  H. Carr,et al.  The Principles of Nuclear Magnetism , 1961 .

[27]  J. Bargon,et al.  Parahydrogen induced polarization , 1997 .

[28]  V. Denysenkov,et al.  High-field dynamic nuclear polarization in aqueous solutions. , 2009, Journal of the American Chemical Society.

[29]  F. Gallagher,et al.  Biomedical applications of hyperpolarized 13C magnetic resonance imaging , 2009 .

[30]  M. Rosay,et al.  Highly efficient, water-soluble polarizing agents for dynamic nuclear polarization at high frequency. , 2013, Angewandte Chemie.

[31]  W. Köckenberger,et al.  The Different Magnetic Resonance Communities Join Forces for Progress in DNP: an Editorial for the Special Issue on DNP , 2012 .

[32]  Krzysztof Kazimierczuk,et al.  Strategy for complete NMR assignment of disordered proteins with highly repetitive sequences based on resolution-enhanced 5D experiments , 2010, Journal of biomolecular NMR.

[33]  Temkin,et al.  Dynamic nuclear polarization with a cyclotron resonance maser at 5 T. , 1993, Physical review letters.

[34]  S. Opella,et al.  Complete resolution of the solid-state NMR spectrum of a uniformly 15N-labeled membrane protein in phospholipid bilayers. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Manfred Spraul,et al.  Cryogenically cooled probes—a leap in NMR technology , 2005 .

[36]  Deniz Sezer,et al.  Dynamic nuclear polarization coupling factors calculated from molecular dynamics simulations of a nitroxide radical in water. , 2009, Physical chemistry chemical physics : PCCP.

[37]  S. Glaser,et al.  Dynamic nuclear polarization at high magnetic fields in liquids. , 2012, Progress in nuclear magnetic resonance spectroscopy.

[38]  R. Griffin,et al.  High-frequency dynamic nuclear polarization using mixtures of TEMPO and trityl radicals. , 2007, The Journal of chemical physics.

[39]  S. Glaser,et al.  Chemical shift correlations from hyperpolarized NMR using a single SHOT. , 2013, Analytical chemistry.

[40]  A. Overhauser,et al.  Paramagnetic Relaxation in Metals , 1953 .

[41]  A. Bax,et al.  An NMR technique for tracing out the carbon skeleton of an organic molecule , 1981 .

[42]  Gil Navon,et al.  Enhancement of Solution NMR and MRI with Laser-Polarized Xenon , 1996, Science.

[43]  R. Griffin,et al.  Overhauser effects in insulating solids. , 2014, The Journal of chemical physics.

[44]  D. Goldfarb,et al.  Dynamic Nuclear Polarization in the solid state: a transition between the cross effect and the solid effect. , 2012, Physical chemistry chemical physics : PCCP.

[45]  I. Bertini,et al.  On the use of ultracentrifugal devices for sedimented solute NMR , 2012, Journal of biomolecular NMR.

[46]  Zoltan Kovacs,et al.  Hyperpolarized (89)Y offers the potential of direct imaging of metal ions in biological systems by magnetic resonance. , 2007, Journal of the American Chemical Society.

[47]  G. Khutsishvili Reviews of Topical Problems: Spin Diffusion , 1966 .

[48]  J. Maan,et al.  Strategies for solid-state NMR in high-field Bitter and hybrid magnets , 2003 .

[49]  S. Opella,et al.  Structure determination of membrane proteins in their native phospholipid bilayer environment by rotationally aligned solid-state NMR spectroscopy. , 2013, Accounts of chemical research.

[50]  R. Griffin,et al.  High frequency dynamic nuclear polarization. , 2013, Accounts of chemical research.

[51]  Shinji Matsumoto,et al.  HTS-NMR: Present Status and Future Plan , 2010, IEEE Transactions on Applied Superconductivity.

[52]  K. Kazimierczuk,et al.  Random sampling in multidimensional NMR spectroscopy. , 2010, Progress in nuclear magnetic resonance spectroscopy.

[53]  E. R. Andrew Spin Temperature and Nuclear Magnetic Resonance in Solids , 1971 .

[54]  A. Sherry,et al.  BDPA: an efficient polarizing agent for fast dissolution dynamic nuclear polarization NMR spectroscopy. , 2011, Chemistry.

[55]  P. Schanda,et al.  UltraSOFAST HMQC NMR and the repetitive acquisition of 2D protein spectra at Hz rates. , 2007, Journal of the American Chemical Society.

[56]  Ivano Bertini,et al.  Solid-state NMR of proteins sedimented by ultracentrifugation , 2011, Proceedings of the National Academy of Sciences.

[57]  P. Woskov,et al.  Microwave field distribution in a magic angle spinning dynamic nuclear polarization NMR probe. , 2011, Journal of magnetic resonance.

[58]  C. Hilty,et al.  Time-resolved dynamic nuclear polarization enhanced NMR spectroscopy. , 2008, Angewandte Chemie.

[59]  Shahila Mehboob,et al.  Nanomole-scale Protein Solid-state NMR by Breaking Intrinsic 1H-T1 Boundaries , 2009, Nature Methods.

[60]  G. Bodenhausen,et al.  Boosting Dissolution Dynamic Nuclear Polarization by Cross Polarization. , 2013, The journal of physical chemistry letters.

[61]  T. Walker,et al.  Spin-exchange optical pumping of noble-gas nuclei , 1997 .

[62]  L. Kay Solution NMR spectroscopy of supra-molecular systems, why bother? A methyl-TROSY view. , 2011, Journal of magnetic resonance.

[63]  Y. Ishii,et al.  Elucidating connectivity and metal-binding structures of unlabeled paramagnetic complexes by 13C and 1H solid-state NMR under fast magic angle spinning. , 2007, The journal of physical chemistry. B.

[64]  K. D. Atkinson,et al.  Iridium N-Heterocyclic Carbene Complexes as Efficient Catalysts for Magnetization Transfer from para-Hydrogen , 2011, Journal of the American Chemical Society.

[65]  C. Dobson,et al.  High-resolution nitrogen-15 nuclear magnetic resonance studies of alpha-lytic protease in solid state. Direct comparison of enzyme structure in solution and in the solid state. , 1984, Biochemistry.

[66]  R G Griffin,et al.  Solid-state 13C NMR detection of a perturbed 6-s-trans chromophore in bacteriorhodopsin. , 1985, Biochemistry.

[67]  R. Griffin,et al.  High-field dynamic nuclear polarization with high-spin transition metal ions. , 2011, Journal of the American Chemical Society.

[68]  R. Riek,et al.  Transverse Relaxation-Optimized Spectroscopy (TROSY) for NMR Studies of Aromatic Spin Systems in 13C-Labeled Proteins , 1998 .

[69]  L. Kay,et al.  New developments in isotope labeling strategies for protein solution NMR spectroscopy. , 2000, Current opinion in structural biology.

[70]  A. Sherry,et al.  Sensitivity enhancement of multidimensional NMR experiments by paramagnetic relaxation effects. , 2006, Journal of the American Chemical Society.

[71]  V. Denysenkov,et al.  High-field liquid state NMR hyperpolarization: a combined DNP/NMRD approach. , 2014, Physical chemistry chemical physics : PCCP.

[72]  A P M Kentgens,et al.  Quantitative analysis of high field liquid state Dynamic Nuclear Polarization. , 2011, Physical chemistry chemical physics : PCCP.

[73]  T. Cross,et al.  Solid state NMR strategy for characterizing native membrane protein structures. , 2013, Accounts of chemical research.

[74]  A. Rosato,et al.  SedNMR: a web tool for optimizing sedimentation of macromolecular solutes for SSNMR , 2013, Journal of Biomolecular NMR.

[75]  A. Feintuch,et al.  Dynamic nuclear polarization assisted spin diffusion for the solid effect case. , 2011, The Journal of chemical physics.

[76]  V. Orekhov,et al.  Analysis of non-uniformly sampled spectra with multi-dimensional decomposition. , 2011, Progress in nuclear magnetic resonance spectroscopy.

[77]  Andrew G. Webb,et al.  Dielectric Materials in Magnetic Resonance , 2011 .

[78]  Christian Scheuerlein,et al.  Isotropic round-wire multifilament cuprate superconductor for generation of magnetic fields above 30 T. , 2014, Nature materials.

[79]  G. Wider,et al.  Managing the solvent water polarization to obtain improved NMR spectra of large molecular structures , 2005, Journal of biomolecular NMR.

[80]  G. Nishijima,et al.  Achievement of 1020MHz NMR. , 2015, Journal of magnetic resonance.

[81]  B. Brandt,et al.  Automated transfer and injection of hyperpolarized molecules with polarization measurement prior to in vivo NMR , 2013, NMR in biomedicine.

[82]  Gisela Guthausen,et al.  Field dependent dynamic nuclear polarization with radicals in aqueous solution. , 2008, Journal of the American Chemical Society.

[83]  Christian Griesinger,et al.  Heteronuclear multidimensional NMR experiments for the structure determination of proteins in solution employing pulsed field gradients , 1999 .

[84]  M. Gangoda,et al.  The influence of hydration on the conformation of bovine serum albumin studied by solid‐state 13C‐nmr spectroscopy , 1993, Biopolymers.

[85]  P. Larson,et al.  Multi-band frequency encoding method for metabolic imaging with hyperpolarized [1-(13)C]pyruvate. , 2011, Journal of magnetic resonance.

[86]  Dietmar Stehlik,et al.  Dynamic Nuclear Polarization in Liquids , 1968 .

[87]  M. Borghini SPIN-TEMPERATURE MODEL OF NUCLEAR DYNAMIC POLARIZATION USING FREE RADICALS. , 1968 .

[88]  C. Hwang,et al.  Phenomenological Model for the New Effect in Dynamic Polarization , 1967 .

[89]  D. Larbalestier,et al.  High Field Magnets With HTS Conductors , 2010, IEEE Transactions on Applied Superconductivity.

[90]  R. Griffin,et al.  High-resolution solid-state NMR structure of a 17.6 kDa protein. , 2010, Journal of the American Chemical Society.

[91]  Andrew J. Nieuwkoop,et al.  Solid-state NMR analysis of membrane proteins and protein aggregates by proton detected spectroscopy , 2012, Journal of Biomolecular NMR.

[92]  I. Bertini,et al.  SedNMR: on the edge between solution and solid-state NMR. , 2013, Accounts of chemical research.

[93]  R. Griffin,et al.  Solid-state 13C NMR study of a transglutaminase-inhibitor adduct. , 1993, Biochemistry.

[94]  L. Kay,et al.  Methyl TROSY: explanation and experimental verification , 2003 .

[95]  T. Takao,et al.  Effect of YBCO-Coil Shape on the Screening Current-Induced Magnetic Field Intensity , 2010, IEEE Transactions on Applied Superconductivity.

[96]  L. Kay,et al.  Bringing dynamic molecular machines into focus by methyl-TROSY NMR. , 2014, Annual review of biochemistry.

[97]  T. Swiet Optimal electric fields for different sample shapes in high resolution NMR spectroscopy. , 2005 .

[98]  Peter. Atkins,et al.  Physical chemistry for the life sciences / Peter Atkins, Julio de Paula. , 2006 .

[99]  Gerhard Wagner,et al.  Non-uniformly sampled double-TROSY hNcaNH experiments for NMR sequential assignments of large proteins. , 2006, Journal of the American Chemical Society.

[100]  Ivano Bertini,et al.  13C–13C NOESY spectra of a 480 kDa protein: solution NMR of ferritin , 2007, Journal of biomolecular NMR.

[101]  T. Glass,et al.  The flow transfer of a bolus with 1H dynamic nuclear polarization from low to high magnetic fields , 1989 .

[102]  Rolf Gruetter,et al.  Hyperpolarized lithium‐6 as a sensor of nanomolar contrast agents , 2009, Magnetic resonance in medicine.

[103]  R G Griffin,et al.  High field dynamic nuclear polarization--the renaissance. , 2010, Physical chemistry chemical physics : PCCP.

[104]  M. Yoshikawa,et al.  Operation of a 500 MHz high temperature superconducting NMR: towards an NMR spectrometer operating beyond 1 GHz. , 2010, Journal of magnetic resonance.

[105]  C. Luchinat,et al.  Overhauser DNP with 15N labelled Frémy's salt at 0.35 Tesla. , 2012, Physical chemistry chemical physics : PCCP.

[106]  E. Hahn,et al.  Nuclear Double Resonance in the Rotating Frame , 1962 .

[107]  R. Griffin,et al.  Dynamic Nuclear Polarization of 1H, 13C, and 59Co in a Tris(ethylenediamine)cobalt(III) Crystalline Lattice Doped with Cr(III) , 2014, Journal of the American Chemical Society.

[108]  J S Petersson,et al.  EPR and DNP properties of certain novel single electron contrast agents intended for oximetric imaging. , 1998, Journal of magnetic resonance.

[109]  C. Copéret,et al.  Dynamic nuclear polarization surface enhanced NMR spectroscopy. , 2013, Accounts of chemical research.

[110]  G. Bodenhausen,et al.  Drug Screening Boosted by Hyperpolarized Long-Lived States in NMR , 2014, ChemMedChem.

[111]  Douglas C. Maus,et al.  Polarization-enhanced NMR spectroscopy of biomolecules in frozen solution. , 1997, Science.

[112]  R. Riek,et al.  [13C,13C]- and [13C,1H]-TROSY in a Triple Resonance Experiment for Ribose−Base and Intrabase Correlations in Nucleic Acids1 , 2001 .

[113]  C. Hilty,et al.  Protein folding studied by dissolution dynamic nuclear polarization. , 2013, Angewandte Chemie.

[114]  Christoffer Laustsen,et al.  Dynamic nuclear polarization and optimal control spatial-selective 13C MRI and MRS. , 2013, Journal of magnetic resonance.

[115]  P. Larson,et al.  Metabolic Imaging of Patients with Prostate Cancer Using Hyperpolarized [1-13C]Pyruvate , 2013, Science Translational Medicine.

[116]  W. Brey,et al.  High-field NMR using resistive and hybrid magnets. , 2008, Journal of magnetic resonance.

[117]  T. Laue,et al.  Modern applications of analytical ultracentrifugation. , 1999, Annual review of biophysics and biomolecular structure.

[118]  R. Griffin,et al.  DNP-Enhanced MAS NMR of Bovine Serum Albumin Sediments and Solutions , 2014, The journal of physical chemistry. B.

[119]  D. Goldfarb,et al.  The interplay between the solid effect and the cross effect mechanisms in solid state ¹³C DNP at 95 GHz using trityl radicals. , 2013, Journal of magnetic resonance.

[120]  Gottfried Otting,et al.  Prospects for lanthanides in structural biology by NMR , 2008, Journal of biomolecular NMR.

[121]  T. Cross,et al.  Solid state NMR: The essential technology for helical membrane protein structural characterization. , 2014, Journal of magnetic resonance.

[122]  J. Granwehr,et al.  Slice-selective single scan proton COSY with dynamic nuclear polarisation. , 2010, Physical chemistry chemical physics : PCCP.

[123]  Rolf Gruetter,et al.  Proton NMR of (15)N-choline metabolites enhanced by dynamic nuclear polarization. , 2009, Journal of the American Chemical Society.

[124]  W. Köckenberger,et al.  Dynamic Nuclear Polarization: New Experimental and Methodology Approaches and Applications in Physics, Chemistry, Biology and Medicine , 2008 .

[125]  J. Ardenkjær-Larsen,et al.  Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[126]  Z. Kovács,et al.  Production and NMR characterization of hyperpolarized (107,109)Ag complexes. , 2012, Angewandte Chemie.

[127]  T. Takao,et al.  Degradation of the performance of a YBCO-coated conductor double pancake coil due to epoxy impregnation , 2010 .

[128]  D. Singel,et al.  High frequency (140 GHz) dynamic nuclear polarization: Polarization transfer to a solute in frozen aqueous solution , 1995 .

[129]  V. Denysenkov,et al.  Liquid state DNP using a 260 GHz high power gyrotron. , 2010, Physical chemistry chemical physics : PCCP.

[130]  A. Webb Advances in Probe Design for Protein NMR , 2006 .

[131]  M. Goldman,et al.  Principles of dynamic nuclear polarisation , 1978 .

[132]  Andreas Hunkeler,et al.  A sedimented sample of a 59 kDa dodecameric helicase yields high-resolution solid-state NMR spectra. , 2012, Angewandte Chemie.

[133]  M. Bennati,et al.  Optimization of dynamic nuclear polarization experiments in aqueous solution at 15 MHz/9.7 GHz: a comparative study with DNP at 140 MHz/94 GHz. , 2010, Physical chemistry chemical physics : PCCP.

[134]  Lucio Frydman,et al.  Ultrafast two-dimensional nuclear magnetic resonance spectroscopy of hyperpolarized solutions , 2007 .

[135]  M. Kainosho,et al.  Stereo-array isotope labeling method for studying protein structure and dynamics. , 2012, Advances in experimental medicine and biology.

[136]  B. Reif,et al.  Structural and Mechanistic Implications of Metal Binding in the Small Heat-shock Protein αB-crystallin* , 2011, The Journal of Biological Chemistry.

[137]  Jürgen Hennig,et al.  Fast multiecho balanced SSFP metabolite mapping of 1H and hyperpolarized 13C compounds , 2009, Magnetic Resonance Materials in Physics, Biology and Medicine.

[138]  P. Schanda,et al.  A set of BEST triple-resonance experiments for time-optimized protein resonance assignment. , 2007, Journal of magnetic resonance.

[139]  E. Oldfield,et al.  Nuclear magnetic resonance of heme protein crystals. General aspects. , 1981, The Journal of biological chemistry.

[140]  K. Wüthrich,et al.  Uniform and Residue-specific 15N-labeling of Proteins on a Highly Deuterated Background , 2004, Journal of biomolecular NMR.

[141]  A. S. Parkes,et al.  Revival of Spermatozoa after Vitrification and Dehydration at Low Temperatures , 1949, Nature.

[142]  A. McDermott,et al.  Solid-state NMR on a type III antifreeze protein in the presence of ice. , 2008, Journal of the American Chemical Society.

[143]  Martin O Leach,et al.  Therapeutic target metabolism observed using hyperpolarized 15N choline. , 2008, Journal of the American Chemical Society.

[144]  A. Feintuch,et al.  Theoretical aspects of Dynamic Nuclear Polarization in the solid state - the cross effect. , 2012, Journal of magnetic resonance.

[145]  C. Malloy,et al.  Could 13C MRI assist clinical decision‐making for patients with heart disease? , 2011, NMR in biomedicine.

[146]  A. Redfield,et al.  Nuclear Magnetic Resonance Saturation and Rotary Saturation in Solids , 1955 .

[147]  J. Granwehr,et al.  A dedicated spectrometer for dissolution DNP NMR spectroscopy. , 2010, Physical chemistry chemical physics : PCCP.

[148]  Kathleen S. McGreevy,et al.  NMR of biomolecules : towards mechanistic systems biology , 2012 .

[149]  R. Tycko Solid-state NMR studies of amyloid fibril structure. , 2011, Annual review of physical chemistry.

[150]  Songi Han,et al.  Transmembrane protein activation refined by site-specific hydration dynamics. , 2013, Angewandte Chemie.

[151]  G. Bodenhausen,et al.  Long-lived states to sustain hyperpolarized magnetization , 2009, Proceedings of the National Academy of Sciences.

[152]  W. R. Sheppard,et al.  Design of a Superconducting 32 T Magnet With REBCO High Field Coils , 2012, IEEE Transactions on Applied Superconductivity.

[153]  R. Tycko,et al.  Solid state nuclear magnetic resonance with magic-angle spinning and dynamic nuclear polarization below 25 K. , 2013, Journal of magnetic resonance.

[154]  S. Becker,et al.  High‐Resolution Solid‐State NMR Studies on Uniformly [13C,15N]‐Labeled Ubiquitin , 2005, Chembiochem : a European journal of chemical biology.

[155]  C. Jeffries,et al.  DYNAMIC POLARIZATION OF NUCLEI BY ELECTRON-NUCLEAR DIPOLAR COUPLING IN CRYSTALS. Technical Report No. 6 , 1961 .

[156]  S. Mangani,et al.  Crystallization of soluble proteins in vapor diffusion for x-ray crystallography , 2007, Nature Protocols.

[157]  Hovav Yonatan,et al.  固体におけるダイナミック核分極(DNP)の理論的側面 固体効果 , 2010 .

[158]  Lucio Frydman,et al.  Dissolution DNP NMR with solvent mixtures: substrate concentration and radical extraction. , 2011, Journal of magnetic resonance.

[159]  Timothy F. Havel,et al.  Solution conformation of proteinase inhibitor IIA from bull seminal plasma by 1H nuclear magnetic resonance and distance geometry. , 1985, Journal of molecular biology.

[160]  K. D. Atkinson,et al.  Reversible Interactions with para-Hydrogen Enhance NMR Sensitivity by Polarization Transfer , 2009, Science.

[161]  T. Polenova,et al.  Probing structure and dynamics of protein assemblies by magic angle spinning NMR spectroscopy. , 2013, Accounts of chemical research.

[162]  C. Ramanathan Dynamic Nuclear Polarization and Spin Diffusion in Nonconducting Solids , 2008, 0801.2170.

[163]  S. Kennedy,et al.  Structural effects of hydration: Studies of lysozyme by 13C solids nmr , 1990, Biopolymers.

[164]  R. Griffin,et al.  Dynamic nuclear polarization with a rigid biradical. , 2009, Angewandte Chemie.

[165]  C. Freund,et al.  Development of an antibody-based, modular biosensor for 129Xe NMR molecular imaging of cells at nanomolar concentrations , 2014, Proceedings of the National Academy of Sciences.

[166]  S. Duckett,et al.  The theory and practice of hyperpolarization in magnetic resonance using parahydrogen. , 2012, Progress in nuclear magnetic resonance spectroscopy.

[167]  N. Bloembergen,et al.  On the interaction of nuclear spins in a crystalline lattice , 1949 .

[168]  Charles P. Slichter,et al.  Polarization of Nuclear Spins in Metals , 1953 .

[169]  P. Woskov,et al.  Corrugated waveguide and directional coupler for CW 250-GHz gyrotron DNP experiments , 2005, IEEE Transactions on Microwave Theory and Techniques.

[170]  D. Wollan Dynamic nuclear poladzzttion with an inhomogeneously broadened ESR line. I. Theory , 1976 .

[171]  W. T. Franks,et al.  Cryogenic temperature effects and resolution upon slow cooling of protein preparations in solid state NMR , 2011, Journal of biomolecular NMR.

[172]  H. Oschkinat,et al.  Sample optimization and identification of signal patterns of amino acid side chains in 2D RFDR spectra of the alpha-spectrin SH3 domain. , 2000, Journal of magnetic resonance.

[173]  S. Opella,et al.  Structure determination of membrane proteins by nuclear magnetic resonance spectroscopy. , 2013, Annual review of analytical chemistry.

[174]  F. Marassi,et al.  Membrane protein structure determination in membrana. , 2013, Accounts of chemical research.

[175]  I. Bertini,et al.  NMR properties of sedimented solutes. , 2012, Physical chemistry chemical physics : PCCP.

[176]  Anne K. Schütz,et al.  Hochaufgelöste Festkörper‐NMR‐Spektren einer sedimentierten, nichtkristallinen dodekameren Helicase (59 kDa) , 2012 .

[177]  Lucio Frydman,et al.  Single-scan NMR spectroscopy at arbitrary dimensions. , 2003, Journal of the American Chemical Society.

[178]  C. Hilty,et al.  Rapid sample injection for hyperpolarized NMR spectroscopy. , 2010, Physical chemistry chemical physics : PCCP.

[179]  T. Szyperski,et al.  GFT NMR, a new approach to rapidly obtain precise high-dimensional NMR spectral information. , 2003, Journal of the American Chemical Society.

[180]  R. Griffin,et al.  A 250 GHz gyrotron with a 3 GHz tuning bandwidth for dynamic nuclear polarization. , 2012, Journal of magnetic resonance.

[181]  Y. Ishii,et al.  Sensitivity and resolution enhanced solid-state NMR for paramagnetic systems and biomolecules under very fast magic angle spinning. , 2013, Accounts of chemical research.

[182]  R. Riek,et al.  Attenuated T2 relaxation by mutual cancellation of dipole-dipole coupling and chemical shift anisotropy indicates an avenue to NMR structures of very large biological macromolecules in solution. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[183]  R. Tycko,et al.  Detection of a transient intermediate in a rapid protein folding process by solid-state nuclear magnetic resonance. , 2010, Journal of the American Chemical Society.

[184]  S. Jannin,et al.  Dynamic Nuclear Polarization by Thermal Mixing Under Partial Saturation , 2012 .

[185]  T. Schmugge,et al.  High dynamic polarization of protons , 1965 .

[186]  C. Hilty,et al.  Solution NMR of polypeptides hyperpolarized by dynamic nuclear polarization. , 2011, Analytical chemistry.

[187]  A. Overhauser Polarization of Nuclei in Metals , 1953 .

[188]  Charles H Cunningham,et al.  Spectral–spatial excitation for rapid imaging of DNP compounds , 2011, NMR in biomedicine.

[189]  Paul Schanda,et al.  Speeding up three-dimensional protein NMR experiments to a few minutes. , 2006, Journal of the American Chemical Society.

[190]  C. Hilty,et al.  Nuclear magnetic resonance of hyperpolarized fluorine for characterization of protein-ligand interactions. , 2012, Journal of the American Chemical Society.

[191]  R. Gruetter,et al.  Localized in vivo hyperpolarization transfer sequences , 2012, Magnetic resonance in medicine.

[192]  R. Gruetter,et al.  In Vivo Detection of Brain Krebs Cycle Intermediate by Hyperpolarized Magnetic Resonance , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[193]  C. Hwang,et al.  New Effect in Dynamic Polarization , 1967 .

[194]  I. Felli,et al.  Magic angle spinning NMR of paramagnetic proteins. , 2013, Accounts of chemical research.

[195]  L. Emsley,et al.  Absence of Curie relaxation in paramagnetic solids yields long 1H coherence lifetimes. , 2007, Journal of the American Chemical Society.

[196]  Songi Han,et al.  Quantitative cw Overhauser effect dynamic nuclear polarization for the analysis of local water dynamics. , 2013, Progress in nuclear magnetic resonance spectroscopy.

[197]  Thomas Szyperski,et al.  G-matrix Fourier transform NMR spectroscopy for complete protein resonance assignment. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[198]  Rolf Gruetter,et al.  Scavenging free radicals to preserve enhancement and extend relaxation times in NMR using dynamic nuclear polarization. , 2010, Angewandte Chemie.

[199]  A. Kentgens,et al.  Pushing the limit of liquid-state dynamic nuclear polarization at high field. , 2010, Physical chemistry chemical physics : PCCP.

[200]  K. Takeda,et al.  Paramagnetic shimming for wide-range variable-field NMR. , 2014, Journal of magnetic resonance.

[201]  C. Griesinger,et al.  Evaluation of a Shuttle DNP Spectrometer by Calculating the Coupling and Global Enhancement Factors of l-Tryptophan , 2012 .

[202]  Lucio Frydman,et al.  Real-time multidimensional NMR follows RNA folding with second resolution , 2010, Proceedings of the National Academy of Sciences.

[203]  A. McDermott,et al.  Protein Linewidth and Solvent Dynamics in Frozen Solution NMR , 2012, PloS one.

[204]  C. Jeffries Polarization of Nuclei by Resonance Saturation in Paramagnetic Crystals , 1957 .

[205]  Jürgen Haase,et al.  NMR signal averaging in 62T pulsed fields. , 2011, Journal of magnetic resonance.

[206]  R. Griffin,et al.  Dynamic nuclear polarization of sedimented solutes. , 2013, Journal of the American Chemical Society.