Molecular Modeling of Proteins pp 351-380

Part of the Methods in Molecular Biology book series (MIMB, volume 1215) | Cite as

NMR-Based Modeling and Refinement of Protein 3D Structures

  • Wim F. Vranken
  • Geerten W. Vuister
  • Alexandre M. J. J. Bonvin
Protocol

Abstract

NMR is a well-established method to characterize the structure and dynamics of biomolecules in solution. High-quality structures can now be produced thanks to both experimental advances and computational developments that incorporate new NMR parameters and improved protocols and force fields in the structure calculation and refinement process. In this chapter, we give a short overview of the various types of NMR data that can provide structural information, and then focus on the structure calculation methodology itself. We discuss and illustrate with tutorial examples “classical” structure calculation, refinement, and structure validation approaches.

Key words

NMR Structure calculation Structure refinement Structure validation 

References

  1. 1.
    Wuthrich K (1986) Nmr of proteins and nucleic acids. Wiley, New York, NYGoogle Scholar
  2. 2.
    Neuhaus D, Williamson MP (2000) The nuclear overhauser effect in structural and conformational analysis. Wiley, New York, NYGoogle Scholar
  3. 3.
    Altona C (1996) Vicinal coupling constants and conformation of biomolecules. In Harris DMG, a K R (eds) Encyclopedia of nuclear magnetic resonance. Wiley, London. pp 4909–4922Google Scholar
  4. 4.
    Bax A, Kontaxis G, Tjandra N (2001) Dipolar couplings in macromolecular structure determination. Methods Enzymol 339:127–174PubMedCrossRefGoogle Scholar
  5. 5.
    Bertini I, Luchinat C, Parigi G (2012) Towards mechanistic systems biology. Wiley-VCH Verlag GmbH, Weinheim, Germany. pp 154–171Google Scholar
  6. 6.
    Cavalli A, Salvatella X, Dobson CM, Vendruscolo M (2007) Protein structure determination from NMR chemical shifts. Proc Natl Acad Sci U S A 104:9615–9620PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Shen Y et al (2008) Consistent blind protein structure generation from NMR chemical shift data. Proc Natl Acad Sci U S A 105:4685–4690PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Wishart DS et al (2008) CS23D: a web server for rapid protein structure generation using NMR chemical shifts and sequence data. Nucleic Acids Res 36:W496–W502PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Güntert P (1998) Structure calculation of biological macromolecules from NMR data. Q Rev Biophys 31:145–237PubMedCrossRefGoogle Scholar
  10. 10.
    Linge JP, Williams MA, Spronk CAEM, Bonvin AMJJ, Nilges M (2003) Refinement of protein structures in explicit solvent. Proteins 50:496–506PubMedCrossRefGoogle Scholar
  11. 11.
    Nederveen AJ et al (2005) RECOORD: a recalculated coordinate database of 500+ proteins from the PDB using restraints from the BioMagResBank. Proteins 59:662–672PubMedCrossRefGoogle Scholar
  12. 12.
    Güntert P (2004) Automated NMR structure calculation with CYANA. Methods Mol Biol 278:353–378PubMedGoogle Scholar
  13. 13.
    Brünger AT et al (1998) Crystallography & NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr D Biol Crystallogr 54:905–921PubMedCrossRefGoogle Scholar
  14. 14.
    Brunger AT (2007) Version 1.2 of the Crystallography and NMR system. Nat Protoc 2:2728–2733PubMedCrossRefGoogle Scholar
  15. 15.
    Doreleijers JF et al (2012) CING: an integrated residue-based structure validation program suite. J Biomol NMR 54:267–283PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Luginbühl P, Szyperski T, Wüthrich K (1995) Statistical basis for the use of 13cα chemical shifts in protein structure determination. J Magn Res 109:92Google Scholar
  17. 17.
    Kuszewski J, Qin J, Gronenborn AM, Clore GM (1995) The impact of direct refinement against 13C alpha and 13C beta chemical shifts on protein structure determination by NMR. J Magn Reson B 106:92–96PubMedCrossRefGoogle Scholar
  18. 18.
    Neal S, Nip AM, Zhang H, Wishart DS (2003) Rapid and accurate calculation of protein 1H, 13C and 15N chemical shifts. J Biomol NMR 26:215–240PubMedCrossRefGoogle Scholar
  19. 19.
    Han B, Liu Y, Ginzinger SW, Wishart DS (2011) SHIFTX2: significantly improved protein chemical shift prediction. J Biomol NMR 50:43–57PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Xu XP, Case DA (2001) Automated prediction of 15N, 13Calpha, 13Cbeta and 13C’ chemical shifts in proteins using a density functional database. J Biomol NMR 21:321–333PubMedCrossRefGoogle Scholar
  21. 21.
    Williamson MP, Kikuchi J, Asakura T (1995) Application of 1H NMR chemical shifts to measure the quality of protein structures. J Mol Biol 247:541–546PubMedGoogle Scholar
  22. 22.
    Meiler J (2003) PROSHIFT: protein chemical shift prediction using artificial neural networks. J Biomol NMR 26:25–37PubMedCrossRefGoogle Scholar
  23. 23.
    Shen Y, Bax A (2010) SPARTA+: a modest improvement in empirical NMR chemical shift prediction by means of an artificial neural network. J Biomol NMR 48:13–22PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Karplus M (1963) Vicinal proton coupling in nuclear magnetic resonance. J Am Chem Soc 85:2870–2871CrossRefGoogle Scholar
  25. 25.
    Kim Y, Prestegard JH (1990) Refinement of the NMR structures for acyl carrier protein with scalar coupling data. Proteins 8:377–385PubMedCrossRefGoogle Scholar
  26. 26.
    Torda AE, Brunne RM, Huber T, Kessler H, Van Gunsteren WF (1993) Structure refinement using time-averaged J-coupling constant restraints. J Biomol NMR 3:55–66PubMedCrossRefGoogle Scholar
  27. 27.
    Wagner G, Wüthrich K (1982) Amide protein exchange and surface conformation of the basic pancreatic trypsin inhibitor in solution. Studies with two-dimensional nuclear magnetic resonance. J Mol Biol 160:343–361PubMedCrossRefGoogle Scholar
  28. 28.
    Pervushin K et al (1998) NMR scalar couplings across Watson-Crick base pair hydrogen bonds in DNA observed by transverse relaxation-optimized spectroscopy. Proc Natl Acad Sci U S A 95:14147–14151PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Cordier F, Rogowski M, Grzesiek S, Bax A (1999) Observation of through-hydrogen-bond 2hJHC' in a perdeuterated protein. J Magnet Res 140:510–512CrossRefGoogle Scholar
  30. 30.
    Bonvin AMJJ, Houben K, Guenneugues M, Kaptein R, Boelens R (2001) Rapid protein fold determination using secondary chemical shifts and cross-hydrogen bond 15N-13C“ scalar couplings (3hbJNC”). J Biomol NMR 21:221–233PubMedCrossRefGoogle Scholar
  31. 31.
    Bax A (2003) Weak alignment offers new NMR opportunities to study protein structure and dynamics. Protein Sci 12:1–16PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Bax A, Grishaev A (2005) Weak alignment NMR: a hawk-eyed view of biomolecular structure. Curr Opin Struct Biol 15:563–570PubMedCrossRefGoogle Scholar
  33. 33.
    Prestegard JH, Bougault CM, Kishore AI (2004) Residual dipolar couplings in structure determination of biomolecules. Chem Rev 104:3519–3540PubMedCrossRefGoogle Scholar
  34. 34.
    Tjandra N, Omichinski JG, Gronenborn AM, Clore GM, Bax A (1997) Use of dipolar 1H-15N and 1H-13C couplings in the structure determination of magnetically oriented macromolecules in solution. Nat Struct Biol 4:732–738PubMedCrossRefGoogle Scholar
  35. 35.
    Fushman D, Varadan R, Assfalg M (2004) Determining domain orientation in macromolecules by using spin-relaxation and residual dipolar coupling measurements. Prog Nucl Magn Reson Spectrosc 44:189–214CrossRefGoogle Scholar
  36. 36.
    Tjandra N, Garrett DS, Gronenborn AM, Bax A, Clore GM (1997) Defining long range order in NMR structure determination from the dependence of heteronuclear relaxation times on rotational diffusion anisotropy. Nat Struct Biol 4:443–449PubMedCrossRefGoogle Scholar
  37. 37.
    Bertini I, Luchinat C, Parigi G, Pierattelli R (2005) NMR spectroscopy of paramagnetic metalloproteins. ChemBioChem 6:1536–1549PubMedCrossRefGoogle Scholar
  38. 38.
    Banci L et al (2004) Paramagnetism-based restraints for Xplor-NIH. J Biomol NMR 28:249–261PubMedCrossRefGoogle Scholar
  39. 39.
    Bertini I, Luchinat C, Parigi G (2002) Paramagnetic constraints: an aid for quick solution structure determination of paramagnetic metalloproteins. Concepts Magn Reson 14:259–286CrossRefGoogle Scholar
  40. 40.
    Schwieters CD, Kuszewski JJ, Tjandra N, Clore GM (2003) The Xplor-NIH NMR molecular structure determination package. J Magnet Res 160:65–73CrossRefGoogle Scholar
  41. 41.
    Güntert P, Mumenthaler C, Wüthrich K (1997) Torsion angle dynamics for NMR structure calculation with the new program DYANA. J Mol Biol 273:283–298PubMedCrossRefGoogle Scholar
  42. 42.
    Hus JC, Marion D, Blackledge M (2000) De novo determination of protein structure by NMR using orientational and long-range order restraints. J Mol Biol 298:927–936PubMedCrossRefGoogle Scholar
  43. 43.
    Case DA et al (2005) The Amber biomolecular simulation programs. J Comput Chem 26:1668–1688PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    van der Spoel D et al (2005) GROMACS: fast, flexible, and free. J Comput Chem 26:1701–1718CrossRefGoogle Scholar
  45. 45.
    Krieger E, Koraimann G, Vriend G (2002) Increasing the precision of comparative models with YASARA NOVA–a self-parameterizing force field. Proteins 47:393–402PubMedCrossRefGoogle Scholar
  46. 46.
    Montelione GT et al (2013) Recommendations of the wwPDB NMR validation task force. Structure 21(9):1563–1570PubMedCrossRefGoogle Scholar
  47. 47.
    Kirchner DK, Güntert P (2011) Objective identification of residue ranges for the superposition of protein structures. BMC Bioinformatics 12:170PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Mao B, Guan R, Montelione GT (2011) Improved technologies now routinely provide protein NMR structures useful for molecular replacement. Structure 19:757–766PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Vuister GW, Fogh RH, Hendrickx PMS, Doreleijers JF, Gutmanas A (2013) An overview of tools for the validation of protein NMR structures. J Biomol NMR 58(4):259–285PubMedCrossRefGoogle Scholar
  50. 50.
    Spronk C, Nabuurs SB, Krieger E (2004) Validation of protein structures derived by NMR spectroscopy. Prog Nucl Magn Reson Spectrosc 45:315–337CrossRefGoogle Scholar
  51. 51.
    van der Schot G et al (2013) Improving 3D structure prediction from chemical shift data. J Biomol NMR 57:27–35PubMedCrossRefGoogle Scholar
  52. 52.
    Rosato A et al (2009) CASD-NMR: critical assessment of automated structure determination by NMR. Nat Methods 6:625–626PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Rosato A et al (2012) Blind testing of routine, fully automated determination of protein structures from NMR data. Structure 20:227–236PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Vranken WF et al (2005) The CCPN data model for NMR spectroscopy: development of a software pipeline. Proteins 59:687–696PubMedCrossRefGoogle Scholar
  55. 55.
    Shen Y, Delaglio F, Cornilescu G, Bax A (2009) TALOS+: a hybrid method for predicting protein backbone torsion angles from NMR chemical shifts. J Biomol NMR 44:213–223PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Cheung M-S, Maguire ML, Stevens TJ, Broadhurst RW (2010) DANGLE: A Bayesian inferential method for predicting protein backbone dihedral angles and secondary structure. J Magn Reson 202:223–233PubMedCrossRefGoogle Scholar
  57. 57.
    Wishart DS, Sykes BD (1994) Chemical shifts as a tool for structure determination. Methods Enzymol 239:363–392PubMedCrossRefGoogle Scholar
  58. 58.
    Berjanskii MV, Wishart DS (2005) A simple method to predict protein flexibility using secondary chemical shifts. J Am Chem Soc 127:14970–14971PubMedCrossRefGoogle Scholar
  59. 59.
    Wassenaar TA, et al (2012) WeNMR: structural biology on the grid. J Grid Comp 10:743–767Google Scholar
  60. 60.
    Huang YJ, Powers R, Montelione GT (2005) Protein NMR recall, precision, and F-measure scores (RPF scores): structure quality assessment measures based on information retrieval statistics. J Am Chem Soc 127:1665–1674PubMedCrossRefGoogle Scholar
  61. 61.
    Guerry P, Herrmann T (2012) Comprehensive automation for NMR structure determination of proteins. Methods Mol Biol 831:429–451PubMedCrossRefGoogle Scholar
  62. 62.
    Linge JP, Habeck M, Rieping W, Nilges M (2003) ARIA: automated NOE assignment and NMR structure calculation. Bioinformatics 19:315–316PubMedCrossRefGoogle Scholar
  63. 63.
    Raman S et al (2010) Accurate automated protein NMR structure determination using unassigned NOESY data. J Am Chem Soc 132:202–207PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Linge JP, O'Donoghue SI, Nilges M (2001) Automated assignment of ambiguous nuclear overhauser effects with ARIA. Methods Enzymol 339:71–90PubMedCrossRefGoogle Scholar
  65. 65.
    Seavey BR, Farr EA, Westler WM, Markley JL (1991) A relational database for sequence-specific protein NMR data. J Biomol NMR 1:217–236PubMedCrossRefGoogle Scholar
  66. 66.
    Bhattacharya A, Tejero R, Montelione GT (2007) Evaluating protein structures determined by structural genomics consortia. Proteins 66:778–795PubMedCrossRefGoogle Scholar
  67. 67.
    Vriend G (1990) WHAT IF: a molecular modeling and drug design program. J Mol Graph 8:52–56PubMedCrossRefGoogle Scholar
  68. 68.
    Laskowski RA, Rullmann J, MacArthur MW (1996) AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR. J Biomol NMR 8:477–486PubMedCrossRefGoogle Scholar
  69. 69.
    Herráez A (2006) Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ 34:255–261PubMedCrossRefGoogle Scholar
  70. 70.
    Koradi R, Billeter M, Wüthrich K (1996) MOLMOL: a program for display and analysis of macromolecular structures. J Mol Graph 14(51–5):29–32Google Scholar
  71. 71.
    Moseley HNB, Sahota G, Montelione GT (2004) Assignment validation software suite for the evaluation and presentation of protein resonance assignment data. J Biomol NMR 28:341–355PubMedCrossRefGoogle Scholar
  72. 72.
    Wang L, Eghbalnia HR, Bahrami A, Markley JL (2005) Linear analysis of carbon-13 chemical shift differences and its application to the detection and correction of errors in referencing and spin system identifications. J Biomol NMR 32:13–22PubMedCrossRefGoogle Scholar
  73. 73.
    Wang L, Markley JL (2009) Empirical correlation between protein backbone 15N and 13C secondary chemical shifts and its application to nitrogen chemical shift re-referencing. J Biomol NMR 44:95–99PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Wang B, Wang Y, Wishart DS (2010) A probabilistic approach for validating protein NMR chemical shift assignments. J Biomol NMR 47:85–99PubMedCrossRefGoogle Scholar
  75. 75.
    Ginzinger SW, Gerick F, Coles M, Heun V (2007) CheckShift: automatic correction of inconsistent chemical shift referencing. J Biomol NMR 39:223–227PubMedCrossRefGoogle Scholar
  76. 76.
    Rieping W, Vranken WF (2010) Validation of archived chemical shifts through atomic coordinates. Proteins 78:2482–2489PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Wim F. Vranken
    • 1
  • Geerten W. Vuister
    • 2
  • Alexandre M. J. J. Bonvin
    • 3
  1. 1.Department of Structural Biology, VIB Structural Biology BrusselsVrije Universiteit BrusselBrusselsBelgium
  2. 2.Department of Biochemistry, School of Biological SciencesUniversity of LeicesterLeicesterUK
  3. 3.Faculty of Science—Chemistry, Bijvoet Center for Biomolecular ResearchUtrecht UniversityUtrechtThe Netherlands

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