Protein Dynamics Revealed by CPMG Dispersion

  • Rieko IshimaEmail author
  • Stefan Bagby
Reference work entry


Since internal motion is essential to enable biomolecular function, it is important to understand the internal motion of proteins by applying biophysical methods. Nuclear magnetic resonance (NMR) methods can be used to probe protein dynamics in a nucleus-specific manner covering motions that occur over a wide range of time scales from the picosecond-nanosecond range to greater than seconds. Among these NMR methods, constant-time (CT) Carr-Purcell-Meiboom-Gill (CPMG) dispersion experiments are often applied to characterize protein equilibrium conformations that interconvert on the microsecond to millisecond time scale through the chemical exchange contribution to the detected transverse relaxation rates. This review covers developments and practical aspects of 15N–backbone CT-CPMG dispersion experiments that are frequently used for biomolecular studies, followed by 13C–methyl CT-CPMG dispersion experiments that are suitable for studies of proteins or assemblies in excess of about 50 kDa. Finally, for the efficient application of CPMG dispersion experiments, other NMR experiments are described that may be useful to cover a wider range of protein dynamics and so permit a more informed implementation and interpretation of CPMG dispersion experiments.


CPMG Dynamics Motion NMR Protein Relaxation 


  1. 1.
    Feynman RP, Leighton RB, Sands M. The Feynman lectures on physics. Boston: Addison-Wesley; 1963.Google Scholar
  2. 2.
    Mulder FA, Skrynnikov NR, Hon B, Dahlquist FW, Kay LE. 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. J Am Chem Soc. 2001;123(5):967–75.CrossRefGoogle Scholar
  3. 3.
    Tollinger M, Skrynnikov NR, Mulder FA, Forman-Kay JD, Kay LE. Slow dynamics in folded and unfolded states of an SH3 domain. J Am Chem Soc. 2001;123(46):11341–52. PubMed PMID: 11707108.CrossRefGoogle Scholar
  4. 4.
    Ishima R, Torchia DA. Extending the range of amide proton relaxation dispersion experiments in proteins using a constant-time relaxation-compensated CPMG approach. J Biomol NMR. 2003;25(3):243–8.CrossRefGoogle Scholar
  5. 5.
    Korzhnev DM, Salvatella X, Vendruscolo M, Di Nardo AA, Davidson AR, Dobson CM, Kay LE Low-populated folding intermediates of Fyn SH3 characterized by relaxation. Nature. 2004;430(6999):586–90.CrossRefGoogle Scholar
  6. 6.
    Korzhnev DM, Kloiber K, Kay LE. Multiple-quantum relaxation dispersion NMR spectroscopy probing millisecond time-scale dynamics in proteins: theory and application. J Am Chem Soc. 2004;126(23):7320–9.CrossRefGoogle Scholar
  7. 7.
    Eisenmesser E, Millet O, Labeikovsky W, Korzhnev D, Wolf-Watz M, Bosco DA, et al. Intrinsic dynamics of an enzyme underlies catalysis. Nature. 2005;438(7064):117–21.CrossRefGoogle Scholar
  8. 8.
    Kovrigin EL, Kempf JG, Grey MJ, Loria JP. Faithful estimation of dynamics parameters from CPMG relaxation dispersion measurements. J Magn Reson. 2006;180(1):83–104.CrossRefGoogle Scholar
  9. 9.
    Jee J, Ishima R, Gronenborn AM. Characterization of specific protein association by (15)N CPMG relaxation dispersion NMR: the GB1(A34F) monomer-dimer equilibrium. J Phys Chem B. 2007;112(19):6008–12.CrossRefGoogle Scholar
  10. 10.
    Koenig SH, Schillinger WE. Nuclear magnetic relaxation dispersion in protein solutions. J Biol Chem. 1969;244:3283–9.Google Scholar
  11. 11.
    Kimmich R. Field cycling in NMR relaxation spectroscopy: applications in biological, chemical and polymer physics. Bull Magn Reson. 1979;1(4):195–218.Google Scholar
  12. 12.
    Noack F. NMR field-cycling spectroscopy: principles and applications. Prog NMR Spectrosc. 1986;18:171–276.CrossRefGoogle Scholar
  13. 13.
    Bertini I, Briganti F, Xia ZC, Luchinat C. Nuclear magnetic relaxation dispersion studies of hexaaqua Mn(II) ions in water-glycerol mixtures. J Magn Reson A. 1993;101(2):198–201.CrossRefGoogle Scholar
  14. 14.
    Hodges MW, Cafiso DS, Polnaszek CF, Lester CC, Bryant RG. Water translational motion at the bilayer interface: an NMR relaxation dispersion measurement. Biophys J. 1997;75(5):2575–9.CrossRefGoogle Scholar
  15. 15.
    Koenig SH, Brown RD. Field-cycling relaxometry of protein solutions and tissue : implications for MRI. Prog NMR Spectrosc. 1990;22:487–567.CrossRefGoogle Scholar
  16. 16.
    Halle B, Denisov VP. A new view of water dynamics in immobilized proteins. Biophys J. 1995;69(1):242–9.CrossRefGoogle Scholar
  17. 17.
    Roberts MF, Redfield AG. Phospholipid bilayer surface configuration probed quantitatively by P-31 field-cycling NMR. Proc Natl Acad Sci USA. 2004;101(49):17066–71.CrossRefGoogle Scholar
  18. 18.
    Kimmich R, Anoardo E. Field-cycling NMR relaxometry. Prog NMR Spectrosc. 2004;44:257–320.CrossRefGoogle Scholar
  19. 19.
    Diakova G, Goddard YA, Korb JP, Bryant RG. Water and backbone dynamics in a hydrated protein. Biophys J. 2010;98(1):138–46.CrossRefGoogle Scholar
  20. 20.
    Loria JP, Berlow RB, Watt ED. Characterization of enzyme motions by solution NMR relaxation dispersion. Acc Chem Res. 2008;41(2):212–21.CrossRefGoogle Scholar
  21. 21.
    Hansen DF, Lundström P, Velyvis A, Kay LE. Quantifying millisecond exchange dynamics in proteins by CPMG relaxation dispersion NMR using side-chain 1H probes. J Am Chem Soc. 2012;134(6):3178–89.CrossRefGoogle Scholar
  22. 22.
    Ishima R. CPMG relaxation dispersion. Methods Mol Biol. 2014;1084:29–49. PubMed PMID: 24061914.CrossRefGoogle Scholar
  23. 23.
    Palmer 3rd AG. Chemical exchange in biomacromolecules: past, present, and future. J Magn Reson. 2014;241:3–17. PubMed PMID: 24656076. Pubmed Central PMCID: 4049312.CrossRefGoogle Scholar
  24. 24.
    Jiang B, Yu B, Zhang X, Liu M, Yang D. A (15)N CPMG relaxation dispersion experiment more resistant to resonance offset and pulse imperfection. J Magn Reson. 2015;257:1–7. PubMed PMID: 26037134.CrossRefGoogle Scholar
  25. 25.
    Yuwen T, Vallurupalli P, Kay LE. Enhancing the sensitivity of CPMG relaxation dispersion to conformational exchange processes by multiple-quantum spectroscopy. Angew Chem Int Ed Engl. 2016;55(38):11490–4. PubMed PMID: 27527986.CrossRefGoogle Scholar
  26. 26.
    Frueh DP, Goodrich AC, Mishra SH, Nichols SR. NMR methods for structural studies of large monomeric and multimeric proteins. Curr Opin Struct Biol. 2013;23(5):734–9. PubMed PMID: 23850141. Pubmed Central PMCID: 3805735.CrossRefGoogle Scholar
  27. 27.
    Clark L, Zahm JA, Ali R, Kukula M, Bian L, Patrie SM, et al. Methyl labeling and TROSY NMR spectroscopy of proteins expressed in the eukaryote Pichia pastoris. J Biomol NMR. 2015;62(3):239–45. PubMed PMID: 26025061. Pubmed Central PMCID: 4496254.CrossRefGoogle Scholar
  28. 28.
    Kerfah R, Plevin MJ, Sounier R, Gans P, Boisbouvier J. Methyl-specific isotopic labeling: a molecular tool box for solution NMR studies of large proteins. Curr Opin Struct Biol. 2015;32:113–22. PubMed PMID: 25881211.CrossRefGoogle Scholar
  29. 29.
    Yadav DK, Lukavsky PJ. NMR solution structure determination of large RNA-protein complexes. Prog Nucl Magn Reson Spectrosc. 2016;97:57–81. PubMed PMID: 27888840.CrossRefGoogle Scholar
  30. 30.
    Carver JP, Richards RE. General 2-site solution for chemical exchange produced dependence of T2 upon Carr-Purcell pulse separation. J Magn Reson. 1972;6(1):89–105. PubMed PMID: ISI:A1972L557600008.Google Scholar
  31. 31.
    Davis DG, Perlman ME, London RE. Direct measurements of the dissociation-rate constant for inhibitor-enzyme complexes via the T-1-rho and T-2 (Cpmg) methods. J Magn Reson Ser B. 1994;104(3):266–75. PubMed PMID: ISI:A1994NX80900008.CrossRefGoogle Scholar
  32. 32.
    Jen J. Chemical exchange and NMR T2 relaxation – multisite case. J Magn Reson. 1978;30(1):111–28. PubMed PMID: ISI:A1978FE41700011.Google Scholar
  33. 33.
    Zinn-Justin S, Berthault P, Guenneugues M, Desvaus H. Off-resonance rf fields in heteronuclear NMR. Application to the study of slow motions. J Biomol NMR. 1997;10(4):363–72.CrossRefGoogle Scholar
  34. 34.
    Loria JP, Rance M, Palmer AG. A relaxation-compensated Carr-Purcell-Meiboom-Gill sequence for characterizing chemical exchange by NMR spectroscopy. J Am Chem Soc. 1999;121(10):2331–2. PubMed PMID: ISI:000079242800047.CrossRefGoogle Scholar
  35. 35.
    Jones JA. Optimal sampling strategies for the measurement of relaxation times in proteins. J Magn Reson. 1997;126(2):283–6. PubMed PMID: ISI:A1997XJ19200018.CrossRefGoogle Scholar
  36. 36.
    Ishima R. Recent Developments in (15)N NMR relaxation studies that probe protein backbone dynamics. Top Curr Chem. 2011;326:99–122.CrossRefGoogle Scholar
  37. 37.
    Skrynnikov NR, Mulder FAA, Hon B, Dahlquist FW, Kay LE. 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. J Am Chem Soc. 2001;123(19):4556–66. PubMed PMID: WOS:000168634700023; English.CrossRefGoogle Scholar
  38. 38.
    Hansen DF, Vallurupalli P, Kay LE. An improved (15)N relaxation dispersion experiment for the measurement of millisecond time-scale dynamics in proteins. J Phys Chem B. 2008;112(19):5898–904. PubMed PMID: WOS:000255649600004; English.CrossRefGoogle Scholar
  39. 39.
    Rennella E, Schuetz AK, Kay LE. Quantitative measurement of exchange dynamics in proteins via (13)C relaxation dispersion of (13)CHD2-labeled samples. J Biomol NMR. 2016;65(2):59–64. PubMed PMID: 27251650.CrossRefGoogle Scholar
  40. 40.
    Mukherjee S, Pondaven SP, Jaroniec CP. Conformational flexibility of a human immunoglobulin light chain variable domain by relaxation dispersion nuclear magnetic resonance spectroscopy: implications for protein misfolding and amyloid assembly. Biochemistry. 2011;50(26):5845–57.CrossRefGoogle Scholar
  41. 41.
    Xu X, Ishima R, Ames JB. Conformational dynamics of recoverin’s Ca2 + −myristoyl switch probed by 15 N NMR relaxation dispersion and chemical shift analysis. Proteins. 2011;79(6):1910–22. PubMed PMID: 21465563. Pubmed Central PMCID: 3092842.CrossRefGoogle Scholar
  42. 42.
    Gadian DG, Robinson FNH. Radiofrequency losses in NMR experiments on electrically conducting samples. J Magn Reson. 1979;34:449–55.Google Scholar
  43. 43.
    Hoult DI, Lauterbur PC. The sensitivity of the zeugmatographic experiment involving human samples. J Magn Reson. 1979;34:425–33.Google Scholar
  44. 44.
    Kelly AE, Ou HD, Withers R, Dotsch V. Low-conductivity buffers for high-sensitivity NMR measurements. J Am Chem Soc. 2002;124(40):12013–9.CrossRefGoogle Scholar
  45. 45.
    Horiuchi T, Takahashi M, Kikuchi J, Yokoyama S, Maeda H. Effect of dielectric properties of solvents on the quality factor for a beyond 900 MHz cryogenic probe model. J Magn Reson. 2005;174:34–42.CrossRefGoogle Scholar
  46. 46.
    Gullion T, Baker DB, Conradi MS. New, compensated carr-purcell sequences. J Magn Reson. 1990;89:479–84.Google Scholar
  47. 47.
    Yip GN, Zuiderweg ER. A phase cycle scheme that significantly suppresses offset-dependent artifacts in the R2-CPMG 15 N relaxation experiment. J Magn Reson. 2004;171(1):25–36.CrossRefGoogle Scholar
  48. 48.
    Bain AD, Anand CK, Nie Z. Exact solution to the Bloch equations and application to the Hahn echo. J Magn Reson. 2010;206(2):227–40.CrossRefGoogle Scholar
  49. 49.
    Bain AD, Anand CK, Nie Z. Exact solution of the CPMG pulse sequence with phase variation down the echo train: application to R2 measurements. J Magn Reson. 2011;209(2):183–94.CrossRefGoogle Scholar
  50. 50.
    Myint W, Cai Y, Schiffer CA, Ishima R. Quantitative comparison of errors in 15 N transverse relaxation rates measured using various CPMG phasing schemes. J Biomol NMR. 2012;53(1):13–23.CrossRefGoogle Scholar
  51. 51.
    Clore GM, Driscoll PC, Wingfield PT, Gronenborn AM. Analysis of the backbone dynamics of interleukin-1 beta using two-dimensional inverse detected heteronuclear 15 N-1H NMR spectroscopy. Biochemistry. 1990;29(32):7387–401.CrossRefGoogle Scholar
  52. 52.
    Mandel AM, Akke M, Palmer AG. Backbone dynamics of Escherichia coli ribonuclease HI – correlations with structure and function in an active enzyme. J Mol Biol. 1995;246(1):144–63. PubMed PMID: ISI:A1995QF77400016.CrossRefGoogle Scholar
  53. 53.
    Goldman M. Interference effects in the relaxation of a pair of unlike spin-1/2 nuclei. J Magn Reson. 1984;60(3):437–52. PubMed PMID: WOS:A1984AAC5000010; English.Google Scholar
  54. 54.
    Peng JW, Thanabal V, Wagner G. Improved accuracy of heteronuclear transverse relaxation-time measurements in macromolecules – elimination of antiphase contributions. J Magn Reson. 1991;95(2):421–7. PubMed PMID: WOS:A1991GN28700021; English.Google Scholar
  55. 55.
    Palmer AG, Skelton NJ, Chazin WJ, Wright PE, Rance M. Suppression of the effects of cross-correlation between dipolar and anisotropic chemical-shift relaxation mechanisms in the measurement of spin-spin relaxation rates. Mol Phys. 1992;75(3):699–711. PubMed PMID: WOS:A1992HG11800014; English.CrossRefGoogle Scholar
  56. 56.
    Kay LE, Nicholson LK, Delaglio F, Bax A, Torchia DA. Pulse sequences for removal of the effects of cross correlation between dipolar and chemical-shift anisotropy relaxation mechanisms on the measurement of heteronuclear T1 and T2 values in proteins. J Magn Reson (1969). 1992;97(2):359–75.CrossRefGoogle Scholar
  57. 57.
    Ishima R, Torchia DA. Error estimation and global fitting in transverse-relaxation dispersion experiments to determine chemical-exchange parameters. J Biomol NMR. 2005;32(1):41–54.CrossRefGoogle Scholar
  58. 58.
    Myint W, Ishima R. Chemical exchange effects during refocusing pulses in constant-time CPMG relaxation dispersion experiments. J Biomol NMR. 2009;45(1–2):207–16. PubMed PMID: 19618276.CrossRefGoogle Scholar
  59. 59.
    Ishima R, Torchia DA. Estimating the time scale of chemical exchange of proteins from measurements of transverse relaxation rates in solution. J Biomol NMR. 1999;14(4):369–72. PubMed PMID: 10526408.CrossRefGoogle Scholar
  60. 60.
    Dizhoor AM, Ray S, Kumar S, Niemi G, Spencer M, Brolley D, et al. Recoverin – a calcium sensitive activator of retinal rod guanylate-cyclase. Science. 1991;251(4996):915–8. PubMed PMID: ISI:A1991EY62900037.CrossRefGoogle Scholar
  61. 61.
    Ames JB, Tanaka T, Stryer L, Ikura M. 3-Dimensional solution structure of myristoylated recoverin – implications for the mechanism of the calcium-myristoyl switch. Faseb J. 1995;9(6):A1385-A. PubMed PMID: ISI:A1995QV27400839.Google Scholar
  62. 62.
    Chen CK, Inglese J, Lefkowitz RJ, Hurley JB. Ca2+-dependent interaction of recoverin with rhodopsin kinase. J Biol Chem. 1995;270(30):18060–6. PubMed PMID: ISI:A1995RM26600066.CrossRefGoogle Scholar
  63. 63.
    Ames JB, Tanaka T, Gordon JI, Ikura M, Stryer L. NMR studies of calcium-bound recoverin containing a polar myristoyl analog. Biophys J. 1997;72(2):TUAM2–TUAM. PubMed PMID: ISI:A1997WE74700651.Google Scholar
  64. 64.
    Tugarinov V, Hwang PM, Ollerenshaw JE, Kay LE. Cross-correlated relaxation enhanced 1H[bond]13C NMR spectroscopy of methyl groups in very high molecular weight proteins and protein complexes. J Am Chem Soc. 2003;125(34):10420–8.CrossRefGoogle Scholar
  65. 65.
    Ollerenshaw JE, Tugarinov V, Skrynnikov NR, Kay LE. Comparison of 13CH3, 13CH2D, and 13CHD2 methyl labeling strategies in proteins. J Biomol NMR. 2005;33(1):25–41. PubMed PMID: 16222555.CrossRefGoogle Scholar
  66. 66.
    Nicholson LK, Kay LE, Baldisseri DM, Arango J, Young PR, Bax A, et al. Dynamics of methyl groups in proteins as studied by proton-detected 13C NMR spectroscopy. Application to the leucine residues of Staphylococcal nuclease. Biochemistry. 1992;31:5253–63.CrossRefGoogle Scholar
  67. 67.
    Mulder FA, Hon B, Mittermaier A, Dahlquist FW, Kay LE. Slow internal dynamics in proteins: application of NMR relaxation dispersion spectroscopy to methyl groups in a cavity mutant of T4 lysozyme. J Am Chem Soc. 2002;124(7):1443–51.CrossRefGoogle Scholar
  68. 68.
    Korzhnev DM, Kloiber K, Kanelis V, Tugarinov V, Kay LE. Probing slow dynamics in high molecular weight proteins by methyl-TROSY NMR spectroscopy: application to a 723-residue enzyme. J Am Chem Soc. 2004;126(12):3964–73.CrossRefGoogle Scholar
  69. 69.
    Lundstrom P, Vallurupalli P, Religa TL, Dahlquist FW, Kay LE. A single-quantum methyl 13C-relaxation dispersion experiment with improved sensitivity. J Biomol NMR. 2007;38(1):79–88. PubMed PMID: 17464570.CrossRefGoogle Scholar
  70. 70.
    Sprangers R, Kay LE. Quantitative dynamics and binding studies of the 20S proteasome by NMR. Nature. 2007;445(7128):618–22.CrossRefGoogle Scholar
  71. 71.
    Ishima R, Louis JM, Torchia DA. Transverse C-13 relaxation of CHD2 methyl isotopmers to detect slow conformational changes of protein side chains. J Am Chem Soc. 1999;121(49):11589–90. PubMed PMID: ISI:000084306600047.CrossRefGoogle Scholar
  72. 72.
    Lundström P, Vallurupalli P, Hansen DF, Kay LE. Isotope labeling methods for studies of excited protein states by relaxation dispersion NMR spectroscopy. Nat Prot. 2009;4:1641–8.CrossRefGoogle Scholar
  73. 73.
    Hansen DF, Vallurupalli P, Lundström P, Neudecker P, Kay LE. Probing chemical shifts of invisible states of proteins with relaxation dispersion NMR spectroscopy: how well can we do? J Am Chem Soc. 2008;130(8):2667–75.CrossRefGoogle Scholar
  74. 74.
    Lundstrom P, Hansen DF, Kay LE. Measurement of carbonyl chemical shifts of excited protein states by relaxation dispersion NMR spectroscopy: comparison between uniformly and selectively (13)C labeled samples. J Biomol NMR. 2008;42(1):35–47. PubMed PMID: 18762869.CrossRefGoogle Scholar
  75. 75.
    Orekhov VY, Korzhnev DM, Kay LE. Double- and zero-quantum NMR relaxation dispersion experiments sampling millisecond time scale dynamics in proteins. J Am Chem Soc. 2004;126(6):1886–91. PubMed PMID: 14871121.CrossRefGoogle Scholar
  76. 76.
    Otten R, Villali J, Kern D, Mulder FA. Probing microsecond time scale dynamics in proteins by methyl (1)H Carr-Purcell-Meiboom-Gill relaxation dispersion NMR measurements. Application to activation of the signaling protein NtrC(r). J Am Chem Soc. 2010;132(47):17004–14. PubMed PMID: 21058670. Pubmed Central PMCID: 2991065.CrossRefGoogle Scholar
  77. 77.
    Li Y, Altorelli NL, Bahna F, Honig B, Shapiro L, Palmer 3rd AG. Mechanism of E-cadherin dimerization probed by NMR relaxation dispersion. Proc Natl Acad Sci USA. 2013;110(41):16462–7. PubMed PMID: 24067646. Pubmed Central PMCID: 3799306.CrossRefGoogle Scholar
  78. 78.
    Ban D, Sabo TM, Griesinger C, Lee D. Measuring dynamic and kinetic information in the previously inaccessible supra-tau(c) window of nanoseconds to microseconds by solution NMR spectroscopy. Molecules. 2013;18(10):11904–37. PubMed PMID: 24077173.CrossRefGoogle Scholar
  79. 79.
    Korzhnev DM, Orekhov VY, Kay LE. Off-resonance R(1rho) NMR studies of exchange dynamics in proteins with low spin-lock fields: an application to a Fyn SH3 domain. J Am Chem Soc. 2005;127(2):713–21.CrossRefGoogle Scholar
  80. 80.
    Massi F, Grey MJ, AG P. Microsecond timescale backbone conformational dynamics in ubiquitin studied with NMR R1rho relaxation experiments. Protein Sci. 2005;14(3):735–42.CrossRefGoogle Scholar
  81. 81.
    Igumenova TI, Palmer AG. Off-resonance TROSY-selected R-1p experiment with improved sensitivity for medium- and high-molecular-weight proteins. J Am Chem Soc. 2006;128(25):8110–1.CrossRefGoogle Scholar
  82. 82.
    Ban D, Gossert AD, Giller K, Becker S, Griesinger C, Lee D. Exceeding the limit of dynamics studies on biomolecules using high spin-lock field strengths with a cryogenically cooled probehead. J Magn Reson. 2012;221:1–4. PubMed PMID: 22743535.CrossRefGoogle Scholar
  83. 83.
    Miloushev VZ, Palmer 3rd AG. R(1rho) relaxation for two-site chemical exchange: general approximations and some exact solutions. J Magn Reson. 2005;177(2):221–7.CrossRefGoogle Scholar
  84. 84.
    Baldwin AJ, Kay LE. An R(1rho) expression for a spin in chemical exchange between two sites with unequal transverse relaxation rates. J Biomol NMR. 2013;55(2):211–8. PubMed PMID: 23340732.CrossRefGoogle Scholar
  85. 85.
    Farrow NA, Muhandiram R, Singer AU, Pascal SM, Kay CM, Gish G, et al. Backbone dynamics of a free and phosphopeptide-complexed Src homology 2 domain studied by 15 N NMR relaxation. Biochemistry. 1994;33(19):5984–6003.CrossRefGoogle Scholar
  86. 86.
    Bouvignies G, Kay LE. Measurement of proton chemical shifts in invisible states of slowly exchanging protein systems by chemical exchange saturation transfer. J Phys Chem B. 2012;116(49):14311–7. PubMed PMID: 23194058.CrossRefGoogle Scholar
  87. 87.
    Fawzi NL, Ying J, Torchia DA, Clore GM. Probing exchange kinetics and atomic resolution dynamics in high-molecular-weight complexes using dark-state exchange saturation transfer NMR spectroscopy. Nat Protoc. 2012;7(8):1523–33. PubMed PMID: 22814391. Pubmed Central PMCID: 3500623.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Structural BiologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  2. 2.Department of Biology and BiochemistryUniversity of BathBathUK

Personalised recommendations