Journal of Mathematical Chemistry

, Volume 56, Issue 8, pp 2525–2536 | Cite as

The structural modeling of EF-hand motifs in parvalbumin

  • Yun Zhao
  • Jianfeng HeEmail author
  • Jing Li
Original Paper


Parvalbumin (Parv) is a typical protein with EF-hand motifs that play an important role in many physiological processes. We present a novel free energy to model the skeletal C\(_\alpha \) chain of the protein from the basic principle of mathematics and physics. Starting from the crystal structure of Parv (PDB code 2PVB), we first analyze the profile of the C\(_\alpha \) bond and torsion angles over the segment that contains the secondary structures. Then the parameters in the energy function are evaluated for the helix ABCD fragment that contains two EF-hand domains in Parv. Meanwhile an eight-soliton configuration at the energy minimum is constructed to model the conformation of ABCD fragment. The deviation of the conformation constructed from the model away from the crystal structure is as small as 1.28 Å. The structural modeling stems from the physical energy, which is a benefit relative to the statistics-based or knowledge-based technologies.


Parvalbumin EF-hand Protein structural modeling Free energy Soliton 



We would like to thank Prof. Antti J. Niemi of Uppsala University, our cooperator in biophysics, for continued discussions on the theory and method. We also thanks the support of the international cooperation project of Beijing Institute of Technology.


  1. 1.
    R.H. Kretsinger, D.J. Nelson, Calcium in biological systems. Coord. Chem. Rev. 18, 29–124 (1976)CrossRefGoogle Scholar
  2. 2.
    R.H. Kretsinger, D. Moncrief, A. Persechini, The EF-hand family of calcium-modulated proteins. Trends Neurosci. 12, 462–467 (1989)CrossRefPubMedGoogle Scholar
  3. 3.
    H. Kawasaki, R.H. Kretsinger, Calcium-binding proteins 1: EF-hands. Protein Profile 1, 343–517 (1994)PubMedGoogle Scholar
  4. 4.
    B.W. Schafer, C.W. Heizmann, The S100 family of EF-hand calcium-binding proteins: functions and pathology. Trends Biochem. Sci. 21, 134–140 (1996)CrossRefPubMedGoogle Scholar
  5. 5.
    A.S. Polans, D. Witkowska, T.L. Heley, D. Amundson, L. Baizer, G. Adamus, Recoverin, a photoreceptor-specific calcium-binding protein, is expressed by the tumor of a patient with cancer-associated retinopathy. Proc. Natl. Acad. Sci. U. S. A. 92, 9176–9180 (1995)CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    P. Vito, E. Lacana, L.D. Adamio, Interfering with apoptosis: Ca\(^{2+}\)-binding protein ALG-2 and Alzheimer’s disease gene ALG-3. Science 271, 521–525 (1996)CrossRefPubMedGoogle Scholar
  7. 7.
    R.H. Kretsinger, C.E. Nockolds, Carp muscle calcium-binding protein. J. Biol. Chem. 248, 3313–3326 (1973)PubMedGoogle Scholar
  8. 8.
    S.J. Opella, D.J. Nelson, O. Jardetzky, Carbon magnetic resonance study of the conformational changes in carp muscle calcium binding parvalbumin. J. Am. Chem. Soc. 96, 7157–7159 (1974)CrossRefPubMedGoogle Scholar
  9. 9.
    A. Cavé, C.M. Dobson, J. Parello, R.J.P. Williams, Conformation mobility within the structure of muscular parvalbumins. An NMR study of the aromatic resonances of phenylalanine residues. FEBS Lett. 65, 190–194 (1976)CrossRefPubMedGoogle Scholar
  10. 10.
    J.P. Declecq, B. Tinant, J. Parello, X-ray structure of a new crystal form of pike 4.10 \(\beta \) parvalbumin. Acta Crystallogr. Sect. D 52, 165–169 (1996)CrossRefGoogle Scholar
  11. 11.
    J.P. Declercq, C. Evrard, V. Lamzin, J. Parello, Crystal structure of the EF-hand parvalbumin at atomic resolution (0.91 Å) and at low temperature (100 K). Evidence for conformational multistates within the hydrophobic core. Protein Sci. 8, 2194–2204 (1999)CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    R.C. Richardson, N.M. King, D.J. Harrington, H. Sun, W.E. Royer, D.J. Nelson, X-ray crystal structure and molecular dynamics simulations of silver hake parvalbumin (isoform B). Protein Sci. 9, 73–82 (2000)CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    S.K. Drake, K.L. Lee, J.J. Falke, Tuning the equilibrium ion affinity and selectivity of the EF-hand calcium binding motif: substitutions at the gateway position. Biochemistry 35, 6697–6705 (1996)CrossRefPubMedGoogle Scholar
  14. 14.
    K. Fahie, R. Pitts, K.M. Elkins, D.J. Nelson, Molecular dynamics study of Ca\(^{2+}\)-binding loop variants of silver hake parvalbumin with aspartic acid at the “Gateway” position. J. Biomol. Struct. Dyn. 19, 821–837 (2002)CrossRefPubMedGoogle Scholar
  15. 15.
    D. Baker, A. Sali, Protein structure prediction and structural genomics. Science 294, 93–96 (2001)CrossRefPubMedGoogle Scholar
  16. 16.
    K.A. Dill, S.B. Ozkan, M.S. shell, T.R. Weikl, The protein folding problem. Annu. Rev. Biophys. 37, 289–316 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    P. Ahlstöm, O. Teleman, B. Jönsson, Molecular dynamics simulation of interfacial water structure and dynamics in a parvalbumin solution. J. Am. Chem. Soc. 110, 4198–4203 (1988)CrossRefGoogle Scholar
  18. 18.
    D. Allouche, J. Parello, Y.H. Sanejouand, Ca\(^{2+}\)/Mg\(^{2+}\) exchange in parvalbumin and other EF-hand proteins. A theoretical study. J. Mol. Biol. 285, 857–873 (1999)CrossRefPubMedGoogle Scholar
  19. 19.
    M.S. Cates, M.L. Teodoro, G.N. Phillops Jr., Molecular mechanisms of calcium and magnesium binding to parvalbumin. Biophys. J. 82, 1133–1146 (2002)CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    A.N. Kucharski, C.E. Scott, J.P. Davis, P.M. Kekenes-Huskey, Understanding ion binding affinity and selectivity in \(\beta \)-parvalbumin unsing molecular dynamics and mean spherical approximation theory. J. Phys. Chem. B 120, 8617–8630 (2016)CrossRefPubMedGoogle Scholar
  21. 21.
    J.F. He, J. Dai, J. Li, X.B. Peng, A.J. Niemi, Aspects of structural landscape of human islet amyloid polypeptide. J. Chem. Phys. 142, 045102 (2015)CrossRefPubMedGoogle Scholar
  22. 22.
    J. Dai, A.J. Niemi, J.F. He, A. Sieradzan, N. Ilieva, Bloch spin waves and emergent structure in protein folding with HIV envelope glycoprotein as an example. Phys. Rev. E 93, 032409 (2016)CrossRefPubMedGoogle Scholar
  23. 23.
    J. Dai, A.J. Niemi, J.F. He, Conformational landscape of an amyloid intra-cellular domain and Landau–Ginzburg–Wilson paradigm in protein dynamics. J. Chem. Phys. 145, 045103 (2016)CrossRefPubMedGoogle Scholar
  24. 24.
    J.J. Liu, J. Dai, J.F. He, A.J. Niemi, N. Ilieva, Multistage modeling of protein dynamics with monomeric Myc oncoprotein as an example. Phys. Rev. E 95, 032406 (2017)CrossRefPubMedGoogle Scholar
  25. 25.
    X. Peng, A. Chenani, S. Hu, Y. Zhou, A. Niemi, A three dimensional visualisation approach to protein heavy-atom structure reconstruction. BMC Struct. Biol. 14, 27 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    S.B. Anfinsen, Principles that govern the folding of protein chains. Science 181, 223–230 (1973)CrossRefPubMedGoogle Scholar
  27. 27.
    I. Sillitoe, T.E. Lewis, A. Cuff, S. Das, P. Ashford, N.L. Dawson, N. Furnham, R.A. Laskowski, D. Lee, J.G. Lees, S. Lehtinen, R.A. Studer, J. Thornton, C.A. Orengo, CATH: comprehensive structural and functional annotations for genome sequences. Nucleic Acids Res. 43(D1), D376–D381 (2015)CrossRefPubMedGoogle Scholar
  28. 28.
    A.G. Murzin, S.E. Brenner, T. Hubbard, C. Chothia, SCOP: a structural classification of proteins database for the investigation of sequences and structures. J. Mol. Biol. 247, 536–540 (1995)PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of PhysicsBeijing Institute of TechnologyBeijingPeople’s Republic of China
  2. 2.Beijing Genetech Pharmaceutical Co. Ltd.BeijingPeople’s Republic of China

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