Advertisement

Biochemistry (Moscow)

, Volume 76, Issue 12, pp 1321–1336 | Cite as

Influence of intramolecular interactions on conformational and dynamic properties of analogs of heptapeptide AFP14–20

  • N. T. MoldogazievaEmail author
  • K. V. Shaitan
  • M. Yu. Antonov
  • I. K. Vinogradova
  • A. A. Terentiev
Article

Abstract

Conformational and dynamic properties of proteins and peptides play an important role in their functioning. However, mechanisms that underlie this influence have not been fully elucidated. In the present work we computationally constructed analogs of heptapeptide AFP14–20 (LDSYQCT) — one of the biologically active sites of human α-fetoprotein (AFP) — to study their conformational and dynamic properties using molecular dynamics simulation. Analogs were obtained by point substitutions of amino acid residues taking into account differences in their physicochemical properties and also on the basis of analysis of amino acid substitutions in the AFP14–20-like motifs revealed in different physiologically active proteins. It is shown that changes in conformational mobility of amino acid residues of analogs are due to disruption or arising of intramolecular interactions that, in turn, determine existence of steric restrictions during rotation around covalent bonds of the peptide backbone. Substitution of an amino acid by another one with significant difference in physicochemical properties may not lead to remarkable changes in conformational and dynamic properties of the peptide if intramolecular interactions remain unchanged.

Key words

α-fetoprotein AFP analogs of heptapeptide AFP14–20 molecular dynamics intramolecular interactions 

Abbreviations

AFP

α-fetoprotein

EGF

epidermal growth factor

MD

molecular dynamics

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Terentiev, A. A., and Moldogazieva, N. T. (2006) Biochemistry (Moscow), 71, 120–132.CrossRefGoogle Scholar
  2. 2.
    Terentiev, A. A. (1997) Vestnik RGMU, 1, 76–79.Google Scholar
  3. 3.
    Terentiev, A. A., Simonova, A. V., Arshinova, S. S., Kulakov, V. V., Bakhus, G. O., Pavlichenkov, A. V., Kudryavtseva, E. V., Bespalova, Zh. D., Ovchinnikov, M. V., Moldogazieva, N. T., and Tagirova, A. K. (2004) Immunologiya, 5, 279–281.Google Scholar
  4. 4.
    Terentiev, A. A., Moldogazieva, N. T., Tagirova, A. K., and Kazimirskaya, V. A. (2004) Russ. J. Immunol., 9, 54.Google Scholar
  5. 5.
    Kazimirsky, A. N., Moldogazieva, N. T., Tagirova, A. N., Poryadin, G. V., Salmasi, J. M., Alexandrova, I. A., and Terentiev, A. A. (2006) Tumor Biol., 27,Suppl. 2, 35.Google Scholar
  6. 6.
    Zaretsky, J. Z., and Wreschner, D. H. (2008) Translat. Oncogenomics, 3, 99–136.Google Scholar
  7. 7.
    Moldogazieva, N. T., and Terentiev, A. A. (2006) Uspekhi Biol. Khim., 46, 99–148.Google Scholar
  8. 8.
    Terentiev, A. A., and Moldogazieva, N. T. (2007) Biochemistry (Moscow), 9, 920–935.CrossRefGoogle Scholar
  9. 9.
    Neduva, V., and Russel, R. B. (2005) FEBS Lett., 579, 3342–3345.PubMedCrossRefGoogle Scholar
  10. 10.
    Terentiev, A. A., and Moldogazieva, N. T. (2007) in Tumor Markers Research Focus (Chang, D. H., ed.) Nova Science Publishers, N. Y., pp. 163–176.Google Scholar
  11. 11.
    Moldogazieva, N. T., Terentiev, A. A., Kazimirsky, A. N., Antonov, M. Yu., and Shaitan, K. V. (2007) Biochemistry (Moscow), 5, 529–539.CrossRefGoogle Scholar
  12. 12.
    Moldogazieva, N. T., Shaitan, K. V., Tereshkina, K. B., Antonov, M. Yu., and Terentiev, A. A. (2007) Biofizika, 4, 611–624.Google Scholar
  13. 13.
    Gohlke, H., Kiel, C., and Case, D. A. (2003) J. Mol. Biol., 330, 891–913.PubMedCrossRefGoogle Scholar
  14. 14.
    Case, D. A., Cheatham, III, T. E., Darden, T., Golhke, H., Lou, R., and Merz, K. M., Jr. (2005) J. Comput. Chem., 26, 1668–1688.PubMedCrossRefGoogle Scholar
  15. 15.
    Boeckmann, B., Blatter, M.-C., Famiglietti, L., Hinz, U., Lane, L., Roechert, B., and Bairoch, A. (2005) Comptes Rendus Biologies, 328, 882–899.PubMedCrossRefGoogle Scholar
  16. 16.
    Benson, D. A., Karsch-Mizrachi, I., Lipman, D. J., Ostell, J., and Wheeler, D. L. (2008) Nucleic Acid Res. (Database issue), D25–30.Google Scholar
  17. 17.
    Lipman, D. J., and Pearson, W. R. (1985) Science, 227, 1435–1441.PubMedCrossRefGoogle Scholar
  18. 18.
    Pearson, W. R., and Lipman, D. J. (1988) Proc. Natl. Acad. Sci. USA, 85, 2444–2448.PubMedCrossRefGoogle Scholar
  19. 19.
    Pearson, W. R. (1990) Methods Enzymol., 183, 63–98.PubMedCrossRefGoogle Scholar
  20. 20.
    Altschul, S. F., Madden, T. L., Schaffer, A. A., Zhang, J., and Zhang, Z. (1997) Nucleic Acids Res., 25, 3389–3402.PubMedCrossRefGoogle Scholar
  21. 21.
    Smith, T. F., and Waterman, M. S. (1981) J. Mol. Biol., 147, 195–197.PubMedCrossRefGoogle Scholar
  22. 22.
    Berman, H. M., Henrick, K., and Nakamura, H. (2003) Nat. Struct. Biol., 10, 980–989.PubMedCrossRefGoogle Scholar
  23. 23.
    Froimowitz, M. (1993) Biotechniques, 14, 1010–1013.PubMedGoogle Scholar
  24. 24.
    Pearlman, D. A., Case, D. A., Caldwell, J. W., Seibel, G. L., and Singh, U. C. (1991) Amber 4.0, University of California, San Francisco.Google Scholar
  25. 25.
    Cornell, W. D., Cieplak, P., Bayly, C., Gould, I. R., and Merz, K. M. (1995) J. Am. Chem. Soc., 117, 5179–5188.CrossRefGoogle Scholar
  26. 26.
    Dashevsky, V. G. (1974) Conformation of Organic Molecules [in Russian], Khimiya, Moscow.Google Scholar
  27. 27.
    Schmidt, M. W., Baldridge, K. K., Boatz, J. A., Elbert, S. T., and Gordon, M. S. (1993) J. Comput. Chem., 14, 1347–1352.CrossRefGoogle Scholar
  28. 28.
    Westerhoff, H., and van Dam, K. (1992) Thermodynamics and Regulation of Transformations of Free Energy in Biosystems [Russian translation], Mir, Moscow.Google Scholar
  29. 29.
    Lemak, A. S., and Balabaev, N. K. (1995) Mol. Simulation, 15, 223–231.CrossRefGoogle Scholar
  30. 30.
    Lemak, A. S., and Balabaev, N. K. (1996) J. Comput. Chem., 17, 1685–1695.CrossRefGoogle Scholar
  31. 31.
    Golo, V. L., and Shaitan, K. V. (2002) Biofizika, 47, 611–617.PubMedGoogle Scholar
  32. 32.
    Ramachandran, G. N., Ramakrishnan, C., and Sasisekharan, V. (1963) J. Mol. Biol., 7, 75–102.CrossRefGoogle Scholar
  33. 33.
    Gowariker, V. R., Viswanathan, N. V., and Shreedhar, J. (1986) Polymer Science, New Age International Ltd., New Dehli.Google Scholar
  34. 34.
    Kyte, J., and Doolittle, R. F. (1982) J. Mol. Biol., 157, 105–132.PubMedCrossRefGoogle Scholar
  35. 35.
    Samanta, U., Bahadur, R. P., and Chakrabarti, P. (2002) Protein Eng., 15, 659–667.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2011

Authors and Affiliations

  • N. T. Moldogazieva
    • 1
    Email author
  • K. V. Shaitan
    • 2
  • M. Yu. Antonov
    • 2
  • I. K. Vinogradova
    • 1
  • A. A. Terentiev
    • 1
  1. 1.Russian State Medical UniversityMoscowRussia
  2. 2.Biological FacultyLomonosov Moscow State UniversityMoscowRussia

Personalised recommendations