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Nuclear Magnetic Resonance-Based Modeling and Refinement of Protein Three-Dimensional Structures and Their Complexes

  • Gloria Fuentes
  • Aalt D. J. van Dijk
  • Alexandre M. J. J. Bonvin
Protocol
Part of the Methods Molecular Biology™ book series (MIMB, volume 443)

Summary

Nuclear magnetic resonance (NMR) has become a well-established method to characterize the structures of biomolecules in solution. High-quality structures are now produced, thanks to both experimental and computational developments, allowing the use of new NMR parameters and improved protocols and force fields in structure calculation and refinement. 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 both “classical” structure calculation and refinement approaches as well as more recently developed protocols for modeling biomolecular complexes.

Keywords

Docking NMR Refinement Structure calculation Validation of structures 
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References

  1. 1.
    1. Wüthrich, K., NMR of proteins and nucleic acids. Wiley: New York, 1986.Google Scholar
  2. 2.
    Neuhaus, D. and Williamson, M. P., The nuclear Overhauser effect in structural and conformational analysis. John Wiley & Sons: 2000.Google Scholar
  3. 3.
    3. Altona, C., Vicinal coupling constants & conformation of biomolecules. In Encyclopedia of Nuclear Magnetic Resonance, Harris, D. M. G. a. K. R., Ed. John Wiley, London: 1996; pp 4909–4922.Google Scholar
  4. 4.
    4. Bax, A., Kontaxis, G. and Tjandra, N. (2001) Dipolar couplings in macromolecular structure determination. Methods in Enzymology 339, 127–174.CrossRefPubMedGoogle Scholar
  5. 5.
    5. Guntert, P. (1998) Structure calculation of biological macromolecules from NMR data. Quarterly Reviews of Biophysics 31, 145–237.CrossRefPubMedGoogle Scholar
  6. 6.
    6. Linge, J. P., Williams, M. A., Spronk, C. A. E. M., Bonvin, A. M. J. J. and Nilges, M. (2003) Refinement of protein structures in explicit solvent. Proteins 50, 496–506.CrossRefPubMedGoogle Scholar
  7. 7.
    7. Nederveen, A. J., Doreleijers, J.F., Vranken, W.F., Miller, Z., Spronk, C.A.E.M, Nabuurs, S.B., Güntert, P., Livny, M., Markley, J.L., Nilges, M., Ulrich, E.L., Kaptein, R., and Bonvin, A.M.J.J. (2005) Recoord: A recalculated coordinates database of 500+ proteins from the pdb using restraint data from the biomagresbank. Proteins: Struc. Funct. & Bioinformatics 59, 662–672.CrossRefGoogle Scholar
  8. 8.
    8. Bonvin, A. M. J. J., Boelens, R. and Kaptein, R. (2005) NMR analysis of protein interactions. Current Opinion in Chemical Biology 9, 501–508.CrossRefPubMedGoogle Scholar
  9. 9.
    9. Zuiderweg, E. R. (2002) Mapping protein-protein interactions in solution by NMR spectroscopy. Biochemistry 41, 1–7.CrossRefPubMedGoogle Scholar
  10. 10.
    10. van Dijk, A. D. J., Boelens, R., and Bonvin, A. M. J. J. (2005) Data-driven docking for the study of biomolecular complexes. Febs Journal 272, 293–312.CrossRefPubMedGoogle Scholar
  11. 11.
    11. Brunger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse-Kunstleve, R. W, Jiang, J.-S., Kuszewski, J., Nilges, N, Pannu, N.S., Read, R.J., Rice, L.M., Simonson, T., and Warren, GL. (1998) Crystallography and NMR system (CNS): A new software system for macromolecular structure determination. Acta Crystallogr. D Biol. 54, 905–921.CrossRefGoogle Scholar
  12. 12.
    12. Linge, J. P., Habeck, M., Rieping, W. and Nilges, M. (2003) Aria: Automated NOE assignment and NMR structure calculation. Bioinformatics 19, 315–316.CrossRefPubMedGoogle Scholar
  13. 13.
    13. Dominguez, C, Boelens, R. and Bonvin, A. M. J. J. (2003) Haddock: A protein-protein docking approach based on biochemical or biophysical information. Journal of the American Chemical Society 125, 1731–1737.CrossRefPubMedGoogle Scholar
  14. 14.
    14. Neal, S., Nip, A. M., Zhang, H. Y. and Wishart, D. S. (2003) Rapid and accurate calculation of protein h-1, c-13 and n-15 chemical shifts. Journal of Biomolecular NMR 26, 215–240.CrossRefPubMedGoogle Scholar
  15. 15.
    15. Xu, X. P. and Case, D. A. (2001) Automated prediction of 15n, 13cα, 13cβ and 13′ chemical shifts in proteins using a density functional database. Journal of Biomolecular NMR 21, 321–333.CrossRefPubMedGoogle Scholar
  16. 16.
    16. Williamson, M. P., Kikuchi, J. and Asakura, T. (1995) Application of h-1-NMR chemical-shifts to measure the quality of protein structures. Journal of Molecular Biology 247, 541–546.PubMedGoogle Scholar
  17. 17.
    17. Meiler, J. (2003) Proshift: Protein chemical shift prediction using artificial neural networks. Journal of Biomolecular NMR 26, 25–37.CrossRefPubMedGoogle Scholar
  18. 18.
    18. Clore, G. M. and Gronenborn, A. M. (1998) New methods of structure refinement for macromolecular structure determination by NMR. Proceedings-National Academy of Sciences USA 95, 5891–5898.CrossRefGoogle Scholar
  19. 19.
    19. Luginbuehl, P., Szyperski, T. and Wuethrich, K. (1995) Statistical basis for the use of 13cα chemical shifts in protein structure determination. Journal of Magnetic Resonance Series B 109, 229.CrossRefGoogle Scholar
  20. 20.
    20. Kuszewski, J., Qin, J., Gronenborn, A. M. and Clore, M. G. (1995) The impact of direct refinement against 13cα and 13cβ chemical shifts on protein structure determination by NMR. Journal of Magnetic Resonance Series B 106, 92.CrossRefPubMedGoogle Scholar
  21. 21.
    21. Karplus, M. (1963) Vicinal proton coupling in nuclear magnetic resonance. Journal American Chemistry Society 85, 2870–2871.CrossRefGoogle Scholar
  22. 22.
    22. Kim, Y. P., J. H. Prestegard (1990) Refinement of the NMR structures for acyl carrier protein with scalar coupling data. Proteins 8, 377–385.CrossRefPubMedGoogle Scholar
  23. 23.
    23. Torda, A. E., Brunne, R. M., Huber, T. and Kessler, H. (1993) Structure refinement using time-averaged j-coupling constant restraints. Journal of Biomolecular NMR 3, 55.CrossRefPubMedGoogle Scholar
  24. 24.
    24. Wagner, G. and Wüthrich, K (1982) Amide proton exchange and surface conformation of the basic pancreatic trypsin inhibitor in solution. Journal Molecular Biology 160, 343–361.CrossRefGoogle Scholar
  25. 25.
    25. Pervushin, K, Ono, A., Fernandez, C, Szyperski, T., Kainosho, M. and Wuthrich, K. (1998) NMR scalar couplings across Watson-Crick base pair hydrogen bonds in DNA observed by transverse relaxation-optimized spectroscopy. Proceedings of the National Academy of Sciences of the United States of America 95, 14147–14151.CrossRefPubMedGoogle Scholar
  26. 26.
    26. Cordier, F., Rogowski, M., Grzesiek, S. and Bax, A. (1999) Observation of through-hydrogen-bond 2hjhc’ in a perdeuterated protein. Journal of Magnetic Resonance 140, 510–512.CrossRefPubMedGoogle Scholar
  27. 27.
    27. Bonvin, A. M. J. J., Houben, K., Guenneugues, M., Kaptein, R. and Boelens, R. (2001) Rapid protein fold determination using secondary chemical shifts and cross-hydrogen bond 15N-13C scalar couplings (3hbjn′). Journal of Biomolecular NMR 21, 221–233.CrossRefPubMedGoogle Scholar
  28. 28.
    28. Bax, A. (2003) Weak alignment offers new NMR opportunities to study protein structure and dynamics. Protein Science 12, 1–16.CrossRefPubMedGoogle Scholar
  29. 29.
    29. Bax, A. and Grishaev, A. (2005) Weak alignment NMR: A hawk-eyed view of biomolecular structure. Current Opinion in Structural Biology 15, 563–570.CrossRefPubMedGoogle Scholar
  30. 30.
    30. Prestegard, J. H., Bougault, C. M. and Kishore, A. I. (2004) Residual dipolar couplings in structure determination of biomolecules. Chemical Reviews 104, 3519–3540.CrossRefPubMedGoogle Scholar
  31. 31.
    31. Tjandra, N, Omichinski, J. G., Gronenborn, A. M., Clore, G. M. and Bax, A. (1997) Use of dipolar 1h-15 N and 1H-13C couplings in the structure determination of magnetically oriented macromolecules in solution. Nature Structural Biology 4, 732–738.CrossRefPubMedGoogle Scholar
  32. 32.
    32. Fushman, D., Varadan, R., Assfalg, M. and Walker, O. (2004) Determining domain orientation in macromolecules by using spin-relaxation and residual dipolar coupling measurements. Progress in Nuclear Magnetic Resonance Spectroscopy 44, 189–214.CrossRefGoogle Scholar
  33. 33.
    33. Tjandra, N, Garrett, D. S., Gronenborn, A. M., Bax, A. and Clore, G. M. (1997) Defining long range order in NMR structure determination from the dependence of heteronuclear relaxation times on rotational diffusion anisotropy. Nature Structural Biology 4,443–449.CrossRefPubMedGoogle Scholar
  34. 34.
    34. Bertini, I., Luchinat, C., Parigi, G. and Pierattelli, R. (2005) NMR spectroscopy of paramagnetic metalloproteins. Chembiochem 6, 1536–1549.CrossRefPubMedGoogle Scholar
  35. 35.
    35. Banci, L., Bertini, I., Cavallaro, G, Giachetti, A., Luchinat, C. and Parigi, G. (2004) Paramagnetism-based restraints for xplor-nih. Journal of Biomolecular NMR 28, 249–261.CrossRefPubMedGoogle Scholar
  36. 36.
    36. Bertini, I., Luchinat, C. and Parigi, G. (2002) Paramagnetic constraints: An aid for quick solution structure determination of paramagnetic metalloproteins. Concepts in Magnetic Resonance 14, 259–286.CrossRefGoogle Scholar
  37. 37.
    37. Schwieters, C. D., Kuszewski, J. J. and Clore, G. M. (2006) Using xplor-nih for NMR molecular structure determination. Progress in Nuclear Magnetic Resonance Spectroscopy 48,47–62.CrossRefGoogle Scholar
  38. 38.
    38. Guntert, P., Mumenthaler, C. and Wuthrich, K. (1997) Torsion angle dynamics for NMR structure calculation with the new program dyana. Journal of Molecular Biology 273, 283–298.CrossRefPubMedGoogle Scholar
  39. 39.
    39. Hus, J. C, Marion, D. and Blackledge, M. (2000) De novo determination of protein structure by NMR using orientational and long-range order restraints. Journal of Molecular Biology 298, 927–936.CrossRefPubMedGoogle Scholar
  40. 40.
    40. Case, D. A., Cheatham, T. E., Darden, T., Gohlke, H., Luo, R., Merz, K. M., Onufriev, A., Simmerling, C, Wang, B. and Woods, R. J. (2005) The amber biomolecular simulation programs. Journal of Computational Chemistry 26, 1668–1688.CrossRefPubMedGoogle Scholar
  41. 41.
    41. Van der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A. E. and Berendsen, H. J. C. (2005) Gromacs: Fast, flexible, and free. Journal of Computational Chemistry 26,1701–1718.CrossRefGoogle Scholar
  42. 42.
    42. Spronk, C. A. E. M., Nabuurs, S. B., Krieger, E., Vriend, G and Vuister, G W (2004) Validation of protein structures derived by NMR spectroscopy. Progress in Nuclear Magnetic Resonance Spectroscopy 45, 315–337.CrossRefGoogle Scholar
  43. 43.
    43. Clore, G. M. (2000) Accurate and rapid docking of protein-protein complexes on the basis of intermolecular nuclear Overhauser enhancement data and dipolar couplings by rigid body minimization. Proc Natl Acad Sci USA 97, 9021–9025.CrossRefPubMedGoogle Scholar
  44. 44.
    44. Takahashi, H., Nakanishi, T., Kami, K., Arata, Y. and Shimada, I. (2000) A novel NMR method for determining the interfaces of large protein-protein complexes. Nature Structural Biology 7, 220–223.CrossRefPubMedGoogle Scholar
  45. 45.
    45. Sakakura, M., Noba, S., Luchette, P. A., Shimada, I. and Prosser, R. S. (2005) An NMR method for the determination of protein-binding interfaces using dioxygen-induced spin-lattice relaxation enhancement. Journal of the American Chemical Society 127, 5826–5832.CrossRefPubMedGoogle Scholar
  46. 46.
    46. Clore, G M. and Schwieters, C. D. (2003) Docking of protein-protein complexes on the basis of highly ambiguous intermolecular distance restraints derived from 1H/15N chemical shift mapping and backbone 15N-1H residual dipolar couplings using conjoined rigid body/torsion angle dynamics. J Am Chem Soc 125, 2902–2912.CrossRefPubMedGoogle Scholar
  47. 47.
    47. Dobrodumov, A. and Gronenborn, A. M. (2003) Filtering and selection of structural models: Combining docking and NMR. Proteins 53, 18–32.CrossRefPubMedGoogle Scholar
  48. 48.
    48. Fahmy, A. and Wagner, G. (2002) Treedock: A tool for protein docking based on minimizing Van der Waals energies. J Am Chem Soc 124, 1241–1250.CrossRefPubMedGoogle Scholar
  49. 49.
    49. McCoy, M. A. and Wyss, D. F. (2002) Structures of protein-protein complexes are docked using only NMR restraints from residual dipolar coupling and chemical shift perturbations. J Am Chem Soc 124, 2104–2105.CrossRefPubMedGoogle Scholar
  50. 50.
    50. Herrmann, T., Guntert, P. and Wuthrich, K. (2002) Protein NMR structure determination with automated NOE assignment using the new software candid and the torsion angle dynamics algorithm dyana. Journal of Molecular Biology 319, 209–227.CrossRefPubMedGoogle Scholar
  51. 51.
    51. Vranken, W. F., Boucher, W., Stevens, T. J., Fogh, R. H., Pajon, A., Llinas, M., Ulrich, E. L., Markley, J. L., Ionides, J. and Laue, E. D. (2005) The ccpn data model for NMR spectroscopy: Development of a software pipeline. Proteins 59, 687–696.CrossRefPubMedGoogle Scholar
  52. 52.
    52. Cornilescu, G., Delaglio, F. and Bax, A. (1999) Protein backbone angle restraints from searching a database for chemical shift and sequence homology. Journal of Biomolecular NMR 13, 289–302.CrossRefPubMedGoogle Scholar
  53. 53.
    Wishart, D. S. and Sykes, B. D. (1994) Chemical shifts as a tool for structure determination. Methods In Enzymology, 363.Google Scholar
  54. 54.
    54. Linge, J. P., O'Donoghue, S. I. and Nilges, M. (2001) Automated assignment of ambiguous nuclear Overhauser effects with aria. Methods in Enzymology 339, 71–90.CrossRefPubMedGoogle Scholar
  55. 55.
    55. Gilquin, B., Lecoq, A., Desne, F., Guenneugues, M., Zinn-Justin, S. and Menez, A. (1999) Conformational and functional variability supported by the bpti fold: Solution structure of the ca2+ channel blocker calcicludine. Proteins 34, 520–532.CrossRefPubMedGoogle Scholar
  56. 56.
    56. Seavey, B. R., Farr, E. A., Westler, W. M. and Markley, J. L. (1991) A relational database for sequence-specific protein NMR data. Journal Of Biomolecular NMR 1, 217–236.CrossRefPubMedGoogle Scholar
  57. 57.
    57. Laskowski, R. A., Macarthur, M. W., Moss, D. S. and Thornton, J. M. (1993) Procheck—a program to check the stereochemical quality of protein structures. Journal of Applied Crystallography 26, 283–291.CrossRefGoogle Scholar
  58. 58.
    58. Vriend, G. (1990) What if—a molecular modeling and drug design program. Journal of Molecular Graphics 8, 52–56.CrossRefPubMedGoogle Scholar
  59. 59.
    59. Laskowski, R. A., Rullmann, J. A. C., MacArthur, M. W., Kaptein, R. and Thornton, J. M. (1996) Aqua and procheck-NMR: Programs for checking the quality of protein structures solved by NMR. Journal of Biomolecular NMR 8, 477–486.CrossRefPubMedGoogle Scholar
  60. 60.
    60. Koradi, R., Billeter, M. and Wüthrich, K. (1996) Molmol: A program for display and analysis of macromolecular structures. Journal Molecular Graphics 14, 51–55.CrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Gloria Fuentes
    • 1
  • Aalt D. J. van Dijk
    • 1
  • Alexandre M. J. J. Bonvin
    • 1
  1. 1.Bijvoet Center for Biomolecular ResearchUtrecht UniversityUtrechtThe Netherlands

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