Chemical exchange in biomacromolecules: past, present, and future.

The perspective reviews quantitative investigations of chemical exchange phenomena in proteins and other biological macromolecules using NMR spectroscopy, particularly relaxation dispersion methods. The emphasis is on techniques and applications that quantify the populations, interconversion kinetics, and structural features of sparsely populated conformational states in equilibrium with a highly populated ground state. Applications to folding, molecular recognition, catalysis, and allostery by proteins and nucleic acids are highlighted.

[1]  L. Kay,et al.  Intrinsic dynamics of an enzyme underlies catalysis , 2005, Nature.

[2]  L. Kay,et al.  Studying "invisible" excited protein states in slow exchange with a major state conformation. , 2012, Journal of the American Chemical Society.

[3]  J. Jen.  Chemical exchange and nmr T2 relaxation—The multisite case , 1978 .

[4]  L. Kay,et al.  Double- and zero-quantum NMR relaxation dispersion experiments sampling millisecond time scale dynamics in proteins. , 2004, Journal of the American Chemical Society.

[5]  L. Kay,et al.  An NMR experiment for the accurate measurement of heteronuclear spin-lock relaxation rates. , 2002, Journal of the American Chemical Society.

[6]  Francesca Massi,et al.  Solution NMR and computer simulation studies of active site loop motion in triosephosphate isomerase. , 2006, Biochemistry.

[7]  L. Kay,et al.  An exchange-free measure of 15N transverse relaxation: an NMR spectroscopy application to the study of a folding intermediate with pervasive chemical exchange. , 2007, Journal of the American Chemical Society.

[8]  Peter E Wright,et al.  Measurement of protein unfolding/refolding kinetics and structural characterization of hidden intermediates by NMR relaxation dispersion , 2011, Proceedings of the National Academy of Sciences.

[9]  G. Montelione,et al.  2D chemical exchange NMR spectroscopy by proton-detected heteronuclear correlation , 1989 .

[10]  L. Kay,et al.  Measurement of the signs of methyl 13C chemical shift differences between interconverting ground and excited protein states by R1ρ: an application to αB-crystallin , 2012, Journal of Biomolecular NMR.

[11]  K. Lindorff-Larsen,et al.  Atomic-level description of ubiquitin folding , 2013, Proceedings of the National Academy of Sciences.

[12]  Nirbhay N. Yadav,et al.  Chemical exchange saturation transfer (CEST): What is in a name and what isn't? , 2011, Magnetic resonance in medicine.

[13]  L. Kay,et al.  Measurement of signs of chemical shift differences between ground and excited protein states: a comparison between H(S/M)QC and R1ρ methods , 2010, Journal of biomolecular NMR.

[14]  John F Hunt,et al.  Dynamics of ATP-binding cassette contribute to allosteric control, nucleotide binding and energy transduction in ABC transporters. , 2004, Journal of molecular biology.

[15]  T. Oas,et al.  Conformational selection or induced fit: A flux description of reaction mechanism , 2009, Proceedings of the National Academy of Sciences.

[16]  Paul A. Keifer,et al.  Pure absorption gradient enhanced heteronuclear single quantum correlation spectroscopy with improved sensitivity , 1992 .

[17]  M. Hodsdon,et al.  Ligand binding alters the backbone mobility of intestinal fatty acid-binding protein as monitored by 15N NMR relaxation and 1H exchange. , 1997, Biochemistry.

[18]  R. Ghose,et al.  Probing Slow Backbone Dynamics in Proteins Using TROSY-Based Experiments to Detect Cross-Correlated Time-Modulation of Isotropic Chemical Shifts , 2004, Journal of biomolecular NMR.

[19]  Richard R. Ernst,et al.  INVESTIGATION OF EXCHANGE PROCESSES BY TWO-DIMENSIONAL NMR SPECTROSCOPY , 1980 .

[20]  A. Bax,et al.  Measurement of 15N relaxation rates in perdeuterated proteins by TROSY-based methods , 2012, Journal of Biomolecular NMR.

[21]  D. Kern,et al.  Probing Microsecond Time Scale Dynamics in Proteins by Methyl 1H Carr−Purcell−Meiboom−Gill Relaxation Dispersion NMR Measurements. Application to Activation of the Signaling Protein NtrCr , 2010, Journal of the American Chemical Society.

[22]  R. Kaptein,et al.  An Off-resonance Rotating Frame Relaxation Experiment for the Investigation of Macromolecular Dynamics Using Adiabatic Rotations , 1998, Journal of magnetic resonance.

[23]  R. Brüschweiler,et al.  Dynamics of lysine side-chain amino groups in a protein studied by heteronuclear 1H−15N NMR spectroscopy. , 2011, Journal of the American Chemical Society.

[24]  D. Raleigh,et al.  15N R(1ρ) measurements allow the determination of ultrafast protein folding rates [1] , 2000 .

[25]  I. Andricioaei,et al.  Transient Hoogsteen Base Pairs in Canonical Duplex DNA , 2011, Nature.

[26]  A. Zarrine-Afsar,et al.  Φ-Value analysis of a three-state protein folding pathway by NMR relaxation dispersion spectroscopy , 2007, Proceedings of the National Academy of Sciences.

[27]  L. Kay,et al.  A heteronuclear correlation experiment for simultaneous determination of 15N longitudinal decay and chemical exchange rates of systems in slow equilibrium , 1994, Journal of biomolecular NMR.

[28]  Pallav Kosuri,et al.  Partially folded equilibrium intermediate of the villin headpiece HP67 defined by 13C relaxation dispersion , 2009, Journal of biomolecular NMR.

[29]  A. Palmer,et al.  A Markov model for relaxation and exchange in NMR spectroscopy. , 2005, The journal of physical chemistry. B.

[30]  Peter E Wright,et al.  Millisecond timescale fluctuations in dihydrofolate reductase are exquisitely sensitive to the bound ligands , 2010, Proceedings of the National Academy of Sciences.

[31]  K. Saalwächter,et al.  Solid-state NMR approaches to internal dynamics of proteins: from picoseconds to microseconds and seconds. , 2013, Accounts of chemical research.

[32]  I. Campbell,et al.  Dynamic studies of a fibronectin type I module pair at three frequencies: Anisotropic modelling and direct determination of conformational exchange , 1996, Journal of biomolecular NMR.

[33]  S. Tzeng,et al.  Allosteric inhibition through suppression of transient conformational states. , 2013, Nature chemical biology.

[34]  P. Neudecker,et al.  Measuring the signs of 1H(alpha) chemical shift differences between ground and excited protein states by off-resonance spin-lock R(1rho) NMR spectroscopy. , 2009, Journal of the American Chemical Society.

[35]  H. Vogel,et al.  Specific 12CβD212CγD2S13CεHD2 Isotopomer Labeling of Methionine To Characterize Protein Dynamics by 1H and 13C NMR Relaxation Dispersion , 2012, Journal of the American Chemical Society.

[36]  Nicolas L. Fawzi,et al.  Probing exchange kinetics and atomic resolution dynamics in high-molecular-weight complexes using dark-state exchange saturation transfer NMR spectroscopy , 2012, Nature Protocols.

[37]  J. Cavanagh.  Protein NMR Spectroscopy: Principles and Practice , 1995 .

[38]  C. Kroenke,et al.  Longitudinal and Transverse 1H−15N Dipolar/15N Chemical Shift Anisotropy Relaxation Interference: Unambiguous Determination of Rotational Diffusion Tensors and Chemical Exchange Effects in Biological Macromolecules , 1998 .

[39]  R. Richards,et al.  A general two-site solution for the chemical exchange produced dependence of T2 upon the carr-Purcell pulse separation , 1972 .

[40]  P. Wright,et al.  Suppression of the effects of cross-correlation between dipolar and anisotropic chemical shift relaxation mechanisms in the measurement of spin-spin relaxation rates , 1992 .

[41]  A. Palmer,et al.  On the use of the stochastic Liouville equation in nuclear magnetic resonance: Application to R1ρ relaxation in the presence of exchange , 2003 .

[42]  A. Palmer,et al.  Off-resonance TROSY-selected R 1rho experiment with improved sensitivity for medium- and high-molecular-weight proteins. , 2006, Journal of the American Chemical Society.

[43]  Patrik Lundström,et al.  Quantifying millisecond exchange dynamics in proteins by CPMG relaxation dispersion NMR using side-chain 1H probes. , 2012, Journal of the American Chemical Society.

[44]  C. Eichmüller,et al.  A New Amide Proton R1ρ Experiment Permits Accurate Characterization of Microsecond Time-scale Conformational Exchange , 2005, Journal of biomolecular NMR.

[45]  Patrik Lundström,et al.  Off-resonance rotating-frame amide proton spin relaxation experiments measuring microsecond chemical exchange in proteins , 2005, Journal of biomolecular NMR.

[46]  Michele Vendruscolo,et al.  Structure of an Intermediate State in Protein Folding and Aggregation , 2012, Science.

[47]  L. Kay,et al.  Measurement of slow (micros-ms) time scale dynamics in protein side chains by (15)N relaxation dispersion NMR spectroscopy: application to Asn and Gln residues in a cavity mutant of T4 lysozyme. , 2001, Journal of the American Chemical Society.

[48]  H. Al‐Hashimi,et al.  Preparation, resonance assignment, and preliminary dynamics characterization of residue specific 13C/15N-labeled elongated DNA for the study of sequence-directed dynamics by NMR , 2009, Journal of biomolecular NMR.

[49]  Arieh Warshel,et al.  At the dawn of the 21st century: Is dynamics the missing link for understanding enzyme catalysis? , 2010, Proteins.

[50]  L. Kay,et al.  An improved 15N relaxation dispersion experiment for the measurement of millisecond time-scale dynamics in proteins. , 2008, The journal of physical chemistry. B.

[51]  B. Honig,et al.  Dynamic properties of a type II cadherin adhesive domain: implications for the mechanism of strand-swapping of classical cadherins. , 2008, Structure.

[52]  B. Halle,et al.  Using buried water molecules to explore the energy landscape of proteins , 1996, Nature Structural Biology.

[53]  Conformational exchange of aromatic side chains characterized by L-optimized TROSY-selected 13C CPMG relaxation dispersion , 2012, Journal of biomolecular NMR.

[54]  H. S. Gutowsky,et al.  Dissociation, Chemical Exchange, and the Proton Magnetic Resonance in Some Aqueous Electrolytes , 1953 .

[55]  Geoffrey Bodenhausen,et al.  Singlet-state exchange NMR spectroscopy for the study of very slow dynamic processes. , 2007, Journal of the American Chemical Society.

[56]  L. Kay,et al.  Probing slowly exchanging protein systems via 13Cα-CEST: monitoring folding of the Im7 protein , 2013, Journal of Biomolecular NMR.

[57]  A. Palmer,et al.  Characterization of chemical exchange using residual dipolar coupling. , 2007, Journal of the American Chemical Society.

[58]  Oliver F. Lange,et al.  Solution structure of a minor and transiently formed state of a T4 lysozyme mutant , 2011, Nature.

[59]  Dmitry M Korzhnev,et al.  A Transient and Low-Populated Protein-Folding Intermediate at Atomic Resolution , 2010, Science.

[60]  Oliver F. Lange,et al.  Kinetics of conformational sampling in ubiquitin. , 2011, Angewandte Chemie.

[61]  G. Bodenhausen,et al.  Evidence for slow motion in proteins by multiple refocusing of heteronuclear nitrogen/proton multiple quantum coherences in NMR. , 2004, Journal of the American Chemical Society.

[62]  Mark Voorneveld,et al.  Preparation , 2018, Games Econ. Behav..

[63]  L. Kay,et al.  Probing slow time scale dynamics at methyl-containing side chains in proteins by relaxation dispersion NMR measurements: application to methionine residues in a cavity mutant of T4 lysozyme. , 2001, Journal of the American Chemical Society.

[64]  J. Louis,et al.  Carbonyl carbon transverse relaxation dispersion measurements and ms-μs timescale motion in a protein hydrogen bond network , 2004 .

[65]  A. Palmer,et al.  Protein NMR Spectroscopy: principles and practice, 2nd ed. , 2006 .

[66]  Michele Vendruscolo,et al.  Characterization of the interdomain motions in hen lysozyme using residual dipolar couplings as replica-averaged structural restraints in molecular dynamics simulations. , 2013, Biochemistry.

[67]  R. Kaptein,et al.  Microsecond time scale dynamics in the RXR DNA-binding domain from a combination of spin-echo and off-resonance rotating frame relaxation measurements , 1999, Journal of biomolecular NMR.

[68]  A. Palmer,et al.  Multiplet-filtered and gradient-selected zero-quantum TROSY experiments for 13C1H3 methyl groups in proteins , 2011, Journal of biomolecular NMR.

[69]  A. Palmer,et al.  Disulfide bond isomerization in basic pancreatic trypsin inhibitor: multisite chemical exchange quantified by CPMG relaxation dispersion and chemical shift modeling. , 2003, Journal of the American Chemical Society.

[70]  Arthur G. Palmer,et al.  Monitoring Macromolecular Motions on Microsecond to Millisecond Time Scales by R1ρ−R1 Constant Relaxation Time NMR Spectroscopy , 1996 .

[71]  R. Ebright,et al.  Dynamically driven protein allostery , 2006, Nature Structural &Molecular Biology.

[72]  D. A. Bosco,et al.  Structure and dynamics of pin1 during catalysis by NMR. , 2007, Journal of molecular biology.

[73]  Geoffrey Bodenhausen,et al.  Time scales of slow motions in ubiquitin explored by heteronuclear double resonance. , 2012, Journal of the American Chemical Society.

[74]  P. Neudecker,et al.  Probing chemical shifts of invisible states of proteins with relaxation dispersion NMR spectroscopy: how well can we do? , 2008, Journal of the American Chemical Society.

[75]  R. Konrat,et al.  Probing RNA dynamics via longitudinal exchange and CPMG relaxation dispersion NMR spectroscopy using a sensitive 13C-methyl label , 2011, Nucleic acids research.

[76]  Pilong Li,et al.  The feasibility of parameterizing four-state equilibria using relaxation dispersion measurements , 2011, Journal of biomolecular NMR.

[77]  Pramodh Vallurupalli,et al.  Measurement of bond vector orientations in invisible excited states of proteins , 2007, Proceedings of the National Academy of Sciences.

[78]  A. Palmer,et al.  Microsecond timescale backbone conformational dynamics in ubiquitin studied with NMR R1ρ relaxation experiments , 2005, Protein science : a publication of the Protein Society.

[79]  R. Konrat,et al.  Differential multiple-quantum relaxation arising from cross-correlated time-modulation of isotropic chemical shifts , 2000, Journal of biomolecular NMR.

[80]  Patrik Lundström,et al.  Measurement of carbonyl chemical shifts of excited protein states by relaxation dispersion NMR spectroscopy: comparison between uniformly and selectively 13C labeled samples , 2008, Journal of biomolecular NMR.

[81]  Kai J. Kohlhoff,et al.  Using NMR chemical shifts as structural restraints in molecular dynamics simulations of proteins. , 2010, Structure.

[82]  D. Torchia,et al.  Estimating the time scale of chemical exchange of proteins from measurements of transverse relaxation rates in solution , 1999, Journal of Biomolecular NMR.

[83]  H. Al‐Hashimi,et al.  NMR studies of nucleic acid dynamics. , 2013, Journal of magnetic resonance.

[84]  Dmitry M Korzhnev,et al.  Multiple-quantum relaxation dispersion NMR spectroscopy probing millisecond time-scale dynamics in proteins: theory and application. , 2004, Journal of the American Chemical Society.

[85]  M. Tollinger,et al.  Synthesis of (6-(13)C)pyrimidine nucleotides as spin-labels for RNA dynamics. , 2012, Journal of the American Chemical Society.

[86]  A. Palmer,et al.  NMR R1 rho rotating-frame relaxation with weak radio frequency fields. , 2004, Journal of the American Chemical Society.

[87]  D. G. Davis,et al.  Direct measurements of the dissociation-rate constant for inhibitor-enzyme complexes via the T1 rho and T2 (CPMG) methods. , 1994, Journal of magnetic resonance. Series B.

[88]  T. Szyperski,et al.  Aromatic ring-flipping in supercooled water: implications for NMR-based structural biology of proteins. , 2001, Journal of the American Chemical Society.

[89]  L. Kay,et al.  Probing structure in invisible protein states with anisotropic NMR chemical shifts. , 2008, Journal of the American Chemical Society.

[90]  A. Mittermaier,et al.  Concerted dynamics link allosteric sites in the PBX homeodomain. , 2011, Journal of molecular biology.

[91]  Ad Bax,et al.  Rapid recording of 2D NMR spectra without phase cycling. Application to the study of hydrogen exchange in proteins , 1989 .

[92]  L. Kay,et al.  Reconstructing NMR spectra of "invisible" excited protein states using HSQC and HMQC experiments. , 2002, Journal of the American Chemical Society.

[93]  Oleg Trott,et al.  Theoretical study of R(1rho) rotating-frame and R2 free-precession relaxation in the presence of n-site chemical exchange. , 2004, Journal of magnetic resonance.

[94]  L. Kay,et al.  Backbone dynamics of proteins as studied by 15N inverse detected heteronuclear NMR spectroscopy: application to staphylococcal nuclease. , 1989, Biochemistry.

[95]  Patrik Lundström,et al.  CPMG relaxation dispersion NMR experiments measuring glycine 1Hα and 13Cα chemical shifts in the ‘invisible’ excited states of proteins , 2009, Journal of biomolecular NMR.

[96]  D. Kern,et al.  Antiparallel EmrE exports drugs by exchanging between asymmetric structures , 2011, Nature.

[97]  R. Ghose,et al.  Detection of correlated dynamics on multiple timescales by measurement of the differential relaxation of zero- and double-quantum coherences involving sidechain methyl groups in proteins. , 2006, Journal of magnetic resonance.

[98]  A. Palmer,et al.  Effects of ion binding on the backbone dynamics of calbindin D9k determined by 15N NMR relaxation. , 1993, Biochemistry.

[99]  A. Palmer,et al.  A Relaxation-Compensated Carr−Purcell−Meiboom−Gill Sequence for Characterizing Chemical Exchange by NMR Spectroscopy , 1999 .

[100]  Arieh Warshel,et al.  Catalysis by dihydrofolate reductase and other enzymes arises from electrostatic preorganization, not conformational motions , 2011, Proceedings of the National Academy of Sciences.

[101]  A. J. Shaka,et al.  An improved sequence for broadband decoupling: WALTZ-16 , 1983 .

[102]  H. Vogel,et al.  Specific 12 C β D 2 12 C γ D 2 S 13 C ε HD 2 Isotopomer Labeling of Methionine To Characterize Protein Dynamics by 1 H and 13 C NMR Relaxation Dispersion , 2012 .

[103]  S. Mangia,et al.  Probing slow protein dynamics by adiabatic R(1rho) and R(2rho) NMR experiments. , 2010, Journal of the American Chemical Society.

[104]  Paul Gollnick,et al.  Mechanisms of allosteric gene regulation by NMR quantification of microsecond-millisecond protein dynamics. , 2012, Journal of molecular biology.

[105]  B. Honig,et al.  Mechanism of E-cadherin dimerization probed by NMR relaxation dispersion , 2013, Proceedings of the National Academy of Sciences.

[106]  Nicolas L. Fawzi,et al.  Atomic resolution dynamics on the surface of amyloid β protofibrils probed by solution NMR , 2011, Nature.

[107]  S. Mangia,et al.  Heteronuclear Adiabatic Relaxation Dispersion (HARD) for quantitative analysis of conformational dynamics in proteins. , 2012, Journal of magnetic resonance.

[108]  R. Levy,et al.  Protein dynamics and NMR relaxation: comparison of simulations with experiment , 1982, Nature.

[109]  P. Wright,et al.  Fast and accurate fitting of relaxation dispersion data using the flexible software package GLOVE , 2013, Journal of Biomolecular NMR.

[110]  J. Brender,et al.  Functional dynamics in the active site of the ribonuclease binase , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[111]  H. Dyson,et al.  Mechanism of coupled folding and binding of an intrinsically disordered protein , 2007, Nature.

[112]  D E Wemmer,et al.  Two-state allosteric behavior in a single-domain signaling protein. , 2001, Science.

[113]  C. G. Hoogstraten,et al.  Extensive backbone dynamics in the GCAA RNA tetraloop analyzed using 13C NMR spin relaxation and specific isotope labeling. , 2008, Journal of the American Chemical Society.

[114]  T. Muir,et al.  Tuning Protein Autoinhibition by Domain Destabilization , 2011, Nature Structural &Molecular Biology.

[115]  A. Palmer,et al.  An average-magnetization analysis of R 1ρ relaxation outside of the fast exchange limit , 2003 .

[116]  A. Palmer,et al.  Solution NMR spin relaxation methods for characterizing chemical exchange in high-molecular-weight systems. , 2005, Methods in enzymology.

[117]  J. Stivers,et al.  Using the water signal to detect invisible exchanging protons in the catalytic triad of a serine protease , 2011, Journal of biomolecular NMR.

[118]  Donald Hamelberg,et al.  Resolving the complex role of enzyme conformational dynamics in catalytic function , 2012, Proceedings of the National Academy of Sciences.

[119]  H. Jane Dyson,et al.  A distal mutation perturbs dynamic amino acid networks in dihydrofolate reductase. , 2013, Biochemistry.

[120]  Joseph A. Bank,et al.  Supporting Online Material Materials and Methods Figs. S1 to S10 Table S1 References Movies S1 to S3 Atomic-level Characterization of the Structural Dynamics of Proteins , 2022 .

[121]  N. Skrynnikov,et al.  Microsecond time-scale conformational exchange in proteins: using long molecular dynamics trajectory to simulate NMR relaxation dispersion data. , 2012, Journal of the American Chemical Society.

[122]  C Wang,et al.  CPMG sequences with enhanced sensitivity to chemical exchange , 2001, Journal of biomolecular NMR.

[123]  Michael Bieri,et al.  Automated NMR relaxation dispersion data analysis using NESSY , 2011, BMC Bioinformatics.

[124]  D. Raleigh,et al.  Phi-value analysis for ultrafast folding proteins by NMR relaxation dispersion. , 2010, Journal of the American Chemical Society.

[125]  A. Pardi,et al.  Active site dynamics in the lead-dependent ribozyme. , 2000, Biochemistry.

[126]  A. Palmer,et al.  R(1rho) relaxation for two-site chemical exchange: general approximations and some exact solutions. , 2005, Journal of magnetic resonance.

[127]  A. Allerhand.  Analysis of Carr—Purcell Spin‐Echo NMR Experiments on Multiple‐Spin Systems. I. The Effect of Homonuclear Coupling , 1966 .

[128]  D. LeMaster,et al.  Experimentally assessing molecular dynamics sampling of the protein native state conformational distribution. , 2012, Biophysical chemistry.

[129]  G. Wider,et al.  Studies of slow conformational equilibria in macromolecules by exchange of heteronuclear longitudinal 2-spin-order in a 2D difference correlation experiment , 1991 .

[130]  C D Kroenke,et al.  Nuclear magnetic resonance methods for quantifying microsecond-to-millisecond motions in biological macromolecules. , 2001, Methods in enzymology.

[131]  L. Kay,et al.  An R1ρ expression for a spin in chemical exchange between two sites with unequal transverse relaxation rates , 2013, Journal of biomolecular NMR.

[132]  S. Forsén,et al.  Study of Moderately Rapid Chemical Exchange Reactions by Means of Nuclear Magnetic Double Resonance , 1963 .

[133]  A. Gronenborn,et al.  Enhanced accuracy of kinetic information from CT-CPMG experiments by transverse rotating-frame spectroscopy , 2013, Journal of biomolecular NMR.

[134]  John L. Markley,et al.  Simultaneous Quantification and Identification of Individual Chemicals in Metabolite Mixtures by Two-Dimensional Extrapolated Time-Zero 1H−13C HSQC (HSQC0) , 2011, Journal of the American Chemical Society.

[135]  Andrew L. Lee,et al.  Hidden dynamic allostery in a PDZ domain , 2009, Proceedings of the National Academy of Sciences.

[136]  H. Al‐Hashimi,et al.  Probing transient Hoogsteen hydrogen bonds in canonical duplex DNA using NMR relaxation dispersion and single-atom substitution. , 2012, Journal of the American Chemical Society.

[137]  Rieko Ishima,et al.  Accuracy of Optimized Chemical-exchange Parameters Derived by Fitting CPMG R2 Dispersion Profiles when R20a ≠ R20b , 2006, Journal of biomolecular NMR.

[138]  G. Clore,et al.  TROSY-based z-exchange spectroscopy: application to the determination of the activation energy for intermolecular protein translocation between specific sites on different DNA molecules. , 2007, Journal of the American Chemical Society.

[139]  H. Al‐Hashimi,et al.  Extending the range of microsecond-to-millisecond chemical exchange detected in labeled and unlabeled nucleic acids by selective carbon R(1rho) NMR spectroscopy. , 2009, Journal of the American Chemical Society.

[140]  D. Torchia,et al.  Extending the range of amide proton relaxation dispersion experiments in proteins using a constant-time relaxation-compensated CPMG approach , 2003, Journal of biomolecular NMR.

[141]  Patrik Lundström,et al.  Measuring 13Cβ chemical shifts of invisible excited states in proteins by relaxation dispersion NMR spectroscopy , 2009, Journal of biomolecular NMR.

[142]  A. Palmer,et al.  Mapping chemical exchange in proteins with MW > 50 kD. , 2003, Journal of the American Chemical Society.

[143]  A. Pardi,et al.  NMR chemical exchange as a probe for ligand-binding kinetics in a theophylline-binding RNA aptamer. , 2009, Journal of the American Chemical Society.

[144]  A. Palmer,et al.  TROSY-selected ZZ-exchange experiment for characterizing slow chemical exchange in large proteins , 2009, Journal of biomolecular NMR.

[145]  B. Halle,et al.  Transient access to the protein interior: simulation versus NMR. , 2013, Journal of the American Chemical Society.

[146]  Oleg Trott,et al.  R1rho relaxation outside of the fast-exchange limit. , 2002, Journal of magnetic resonance.

[147]  A. Palmer,et al.  Differential multiple quantum relaxation caused by chemical exchange outside the fast exchange limit , 2002, Journal of biomolecular NMR.

[148]  Christopher D. Kroenke,et al.  The Static Magnetic Field Dependence of Chemical Exchange Linebroadening Defines the NMR Chemical Shift Time Scale , 2000 .

[149]  A. J. Shaka,et al.  Computer-optimized decoupling scheme for wideband applications and low-level operation , 1985 .

[150]  Hsin Wang,et al.  Titration and exchange studies of liver fatty acid-binding protein with 13C-labeled long-chain fatty acids. , 2002, Biochemistry.

[151]  Patrik Lundström,et al.  Quantitative analysis of conformational exchange contributions to 1H-15N multiple-quantum relaxation using field-dependent measurements. Time scale and structural characterization of exchange in a calmodulin C-terminal domain mutant. , 2004, Journal of the American Chemical Society.

[152]  P. Wright,et al.  Intramolecular motions of a zinc finger DNA-binding domain from Xfin characterized by proton-detected natural abundance carbon-13 heteronuclear NMR spectroscopy , 1991 .

[153]  D. Case,et al.  Molecular Dynamics Analysis of NMR Relaxation in a Zinc-Finger Peptide , 1992 .

[154]  Christian Griesinger,et al.  Exceeding the limit of dynamics studies on biomolecules using high spin-lock field strengths with a cryogenically cooled probehead. , 2012, Journal of magnetic resonance.

[155]  Paul Schanda,et al.  Direct observation of the dynamic process underlying allosteric signal transmission. , 2009, Journal of the American Chemical Society.

[156]  Patrik Lundström,et al.  Accurate measurement of alpha proton chemical shifts of excited protein states by relaxation dispersion NMR spectroscopy. , 2009, Journal of the American Chemical Society.

[157]  L. Kay,et al.  Measurement of proton chemical shifts in invisible states of slowly exchanging protein systems by chemical exchange saturation transfer. , 2012, The journal of physical chemistry. B.

[158]  O. Teleman,et al.  Backbone dynamics of calbindin D9k: comparison of molecular dynamics simulations and nitrogen-15 NMR relaxation measurements , 1992 .

[159]  K. Wüthrich,et al.  Disulfide bond isomerization in BPTI and BPTI(G36S): an NMR study of correlated mobility in proteins. , 1993, Biochemistry.

[160]  T Szyperski,et al.  Protein dynamics studied by rotating frame 15N spin relaxation times , 1993, Journal of biomolecular NMR.

[161]  D. Raleigh,et al.  Characterizing a partially folded intermediate of the villin headpiece domain under non-denaturing conditions: contribution of His41 to the pH-dependent stability of the N-terminal subdomain. , 2006, Journal of molecular biology.

[162]  Wei Li,et al.  A Dynamic Knockout Reveals That Conformational Fluctuations Influence the Chemical Step of Enzyme Catalysis , 2011, Science.

[163]  Dmitry M Korzhnev,et al.  Probing slow dynamics in high molecular weight proteins by methyl-TROSY NMR spectroscopy: application to a 723-residue enzyme. , 2004, Journal of the American Chemical Society.