Theoretical Chemistry Accounts

, Volume 121, Issue 3–4, pp 197–200

Prediction of NMR order parameters in proteins using weighted protein contact-number model

  • Shao-Wei Huang
  • Chien-Hua Shih
  • Chih-Peng Lin
  • Jenn-Kang Hwang
Regular Article

Abstract

In the NMR experiment, the protein backbone motion can be described by the N–H order parameters. Though protein dynamics is determined by a complex network of atomic interactions, we show that the order parameter of residues can be determined using a very simple method, the weighted protein contact number model. We computed for each Cα atom the number of neighboring Cα atoms weighted by the inverse distance squared between them. We show that the weighted contact number of each residue is directly related to its order parameter. Despite the simplicity of this model, it performs better than the other method. Since we can compute the order parameters directly from the topological properties (such as protein contact number) of protein structures, our study underscores a very direct link between protein topological structure and its dynamics.

Keywords

NMR order parameter Weighted protein contact number Protein dynamics Prediction 

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References

  1. 1.
    Yang LW, Bahar I (2005) Coupling between catalytic site and collective dynamics: a requirement for mechanochemical activity of enzymes. Structure 13: 893–904CrossRefGoogle Scholar
  2. 2.
    Mukherjee M, Dutta K, White MA, Cowburn D, Fox RO (2006) NMR solution structure and backbone dynamics of domain III of the E protein of tick-borne Langat flavivirus suggests a potential site for molecular recognition. Protein Sci 15: 1342–1355CrossRefGoogle Scholar
  3. 3.
    Warshel A (2002) Molecular dynamics simulations of biological reactions. Acc Chem Res 35: 385–395CrossRefGoogle Scholar
  4. 4.
    Berman H, Henrick K, Nakamura H, Markley JL (2007) The worldwide Protein Data Bank (wwPDB): ensuring a single, uniform archive of PDB data. Nucleic Acids Res 35: D301–303CrossRefGoogle Scholar
  5. 5.
    Levitt M, Warshel A (1975) Computer simulation of protein folding. Nature 253: 694–698CrossRefGoogle Scholar
  6. 6.
    McCammon JA, Gelin BR, Karplus M (1977) Dynamics of folded proteins. Nature 267: 585–590CrossRefGoogle Scholar
  7. 7.
    Warshel A (1976) Bicycle-pedal model for the first step in the vision process. Nature 260: 679–683CrossRefGoogle Scholar
  8. 8.
    Warshel A, Parson WW (2001) Dynamics of biochemical and biophysical reactions: insight from computer simulations. Q Rev Biophys 34: 563–679Google Scholar
  9. 9.
    Karplus M, McCammon JA (2002) Molecular dynamics simulations of biomolecules. Nat Struct Biol 9: 646–652CrossRefGoogle Scholar
  10. 10.
    Showalter SA, Bruschweiler R (2007) Validation of molecular dynamics simulations of biomolecules using NMR spin relaxation as benchmarks: application to the AMBER99SB force field. J Chem Theory Comput 3: 961–975CrossRefGoogle Scholar
  11. 11.
    Rueda M, Ferrer-Costa C, Meyer T, Perez A, Camps J, Hospital A, Gelpi JL, Orozco M (2007) A consensus view of protein dynamics. Proc Natl Acad Sci USA 104: 796–801CrossRefGoogle Scholar
  12. 12.
    Zhang F, Bruschweiler R (2002) Contact model for the prediction of NMR N–H order parameters in globular proteins. J Am Chem Soc 124: 12654–12655CrossRefGoogle Scholar
  13. 13.
    Tirion MM (1996) Large amplitude elastic motions in proteins from a single-parameter, atomic analysis. Phys Rev Lett 77: 1905–1908CrossRefGoogle Scholar
  14. 14.
    Bahar I, Atilgan AR, Erman B (1997) Direct evaluation of thermal fluctuations in proteins using a single-parameter harmonic potential. Fold Des 2: 173–181CrossRefGoogle Scholar
  15. 15.
    Ming D, Bruschweiler R (2006) Reorientational contact-weighted elastic network model for the prediction of protein dynamics: comparison with NMR relaxation. Biophys J 90: 3382–3388CrossRefGoogle Scholar
  16. 16.
    Pfeiffer S, Fushman D, Cowburn D (2001) Simulated and NMR-derived backbone dynamics of a protein with significant flexibility: a comparison of spectral densities for the betaARK1 PH domain. J Am Chem Soc 123: 3021–3036CrossRefGoogle Scholar
  17. 17.
    Tjandra N, Feller SE, Pastor RW, Bax A (1995) Rotational diffusion anisotropy of human ubiquitin from 15N NMR relaxation. J Am Chem Soc 117: 12562–12566CrossRefGoogle Scholar
  18. 18.
    Buck M, Boyd J, Redfield C, MacKenzie DA, Jeenes DJ, Archer DB, Dobson CM (1995) Structural determinants of protein dynamics: analysis of 15N NMR relaxation measurements for main-chain and side-chain nuclei of hen egg white lysozyme. Biochemistry 34: 4041–4055CrossRefGoogle Scholar
  19. 19.
    Harata K, Muraki M (1997) X-ray structure of turkey-egg lysozyme complex with tri-N-acetylchitotriose. Lack of binding ability at subsite A. Acta Crystallogr D Biol Crystallogr 53: 650–657CrossRefGoogle Scholar
  20. 20.
    Akke M, Skelton NJ, Kordel J, Palmer AG 3rd, Chazin WJ (1993) Effects of ion binding on the backbone dynamics of calbindin D9k determined by 15N NMR relaxation. Biochemistry 32: 9832–9844CrossRefGoogle Scholar
  21. 21.
    Svensson LA, Thulin E, Forsen S (1992) Proline cis-trans isomers in calbindin D9k observed by X-ray crystallography. J Mol Biol 223: 601–606CrossRefGoogle Scholar
  22. 22.
    Feng W, Tejero R, Zimmerman DE, Inouye M, Montelione GT (1998) Solution NMR structure and backbone dynamics of the major cold-shock protein (CspA) from Escherichia coli: evidence for conformational dynamics in the single-stranded RNA-binding site. Biochemistry 37: 10881–10896CrossRefGoogle Scholar
  23. 23.
    Li Q, Khosla C, Puglisi JD, Liu CW (2003) Solution structure and backbone dynamics of the holo form of the frenolicin acyl carrier protein. Biochemistry 42: 4648–4657CrossRefGoogle Scholar
  24. 24.
    Halle B (2002) Flexibility and packing in proteins. Proc Natl Acad Sci USA 99: 1274–1279CrossRefGoogle Scholar
  25. 25.
    Kristensen SM, Siegal G, Sankar A, Driscoll PC (2000) Backbone dynamics of the C-terminal SH2 domain of the p85[alpha] subunit of phosphoinositide 3-kinase: effect of phosphotyrosine-peptide binding and characterization of slow conformational exchange processes. J Mol Biol 299: 771–788CrossRefGoogle Scholar
  26. 26.
    Yun S, Jang DS, Kim DH, Choi KY, Lee HC (2001) 15N NMR relaxation studies of backbone dynamics in free and steroid-bound Delta 5-3-ketosteroid isomerase from Pseudomonas testosteroni. Biochemistry 40: 3967–3973CrossRefGoogle Scholar
  27. 27.
    Stivers JT, Abeygunawardana C, Mildvan AS (1996) 15N NMR relaxation studies of free and inhibitor-bound 4-oxalocrotonate tautomerase: backbone dynamics and entropy changes of an enzyme upon inhibitor binding. Biochemistry 35: 16036–16047CrossRefGoogle Scholar
  28. 28.
    Redfield C, Boyd J, Smith LJ, Smith RA, Dobson CM (1992) Loop mobility in a four-helix-bundle protein: 15N NMR relaxation measurements on human interleukin-4. Biochemistry 31: 10431–10437CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Shao-Wei Huang
    • 1
  • Chien-Hua Shih
    • 1
  • Chih-Peng Lin
    • 1
  • Jenn-Kang Hwang
    • 1
  1. 1.Institute of BioinformaticsNational Chiao Tung UniversityHsinChuTaiwan, ROC

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