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Journal of Molecular Modeling

, 15:1501 | Cite as

Molecular dynamics simulations and MM–PBSA calculations of the lectin from snowdrop (Galanthus nivalis)

  • Zhen Liu
  • Yizheng ZhangEmail author
Original Paper

Abstract

Galanthus nivalis agglutinin (GNA), a mannose-specific lectin from snowdrop bulbs, is a member of the monocot mannose-specific lectin family and exhibits antiviral activity toward HIV. In the present study, molecular dynamics (MD) simulations were performed to study the interaction between GNA and its carbohydrate ligand over a specific time span. By analysis of the secondary structures, it was observed that the GNA conformation maintains rather stable along the trajectories and the high fluctuations were only centered on the carbohydrate recognition domains. Our MD simulations also reproduced most of the hydrogen bonds observed in the x-ray crystal structure. Furthermore, the obtained MD trajectories were used to estimate the binding free energy of the complex using the molecular mechanics/Poisson Boltzmann surface area (MM-PBSA) method. It was revealed by the inspection of the binding free energy components that the major contributions to the complex stability arose from electrostatic interactions.

Keywords

AMBER Galanthus nivalis agglutinin (GNA) Lectin Molecular dynamics simulations (MD) Molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) 

Notes

Acknowledgments

The authors acknowledge the UCSF (University of California, San Francisco) for providing us the AMBER 9 program package for free. We also thank Dr. Xiao Li for reading the manuscript and his useful suggestions.

Supplementary material

Movie 1

The dynamic characters of GNA were displayed as a movie (MPG 5372 kb)

References

  1. 1.
    Van Damme EJM, Peumans WJ, Barre A, Rouge P (1998) Plant lectins: a composite of several distinct families of structurally and evolutionary related proteins with diverse biological roles. Crit Rev Plant Sci 17:575–692CrossRefGoogle Scholar
  2. 2.
    Van Damme EJM, Nakamura-Tsuruta S, Smith DF, Ongenaert M, Winter HC, Rouge P, Goldstein IJ, Mo H, Kominami J, Culerrier R, Barre A, Hirabayashi J, Peumans WJ (2007) Phylogenetic and specificity studies of two-domain GNA-related lectins: generation of multispecificity through domain duplication and divergent evolution. Biochem J 404:51–61CrossRefGoogle Scholar
  3. 3.
    Van Damme EJ, Kaku H, Perini F, Goldstein IJ, Peeters B, Yagi F, Decock B, Peumans WJ (1991) Biosynthesis, primary structure and molecular cloning of snowdrop (Galanthus nivalis L) lectin. Eur J Biochem 202:23–30CrossRefGoogle Scholar
  4. 4.
    Shibuya N, Goldstein IJ, van Damme EJ, Peumans WJ (1988) Binding properties of a mannose-specific lectin from the snowdrop (Galanthus nivalis) bulb. J Biol Chem 263:728–734Google Scholar
  5. 5.
    Wright CS, Hester G (1996) The 2.0 A structure of a cross-linked complex between snowdrop lectin and a branched mannopentaose: evidence for two unique binding modes. Structure 4:1339–1352CrossRefGoogle Scholar
  6. 6.
    Hester G, Kaku H, Goldstein IJ, Wright CS (1995) Structure of mannose-specific snowdrop (Galanthus nivalis) lectin is representative of a new plant lectin family. Nat Struct Biol 2:472–479CrossRefGoogle Scholar
  7. 7.
    Hester G, Wright CS (1996) The mannose-specific bulb lectin from Galanthus nivalis (snowdrop) binds mono- and dimannosides at distinct sites. Structure analysis of refined complexes at 2.3 Å and 3.0 Å resolution. J Mol Biol 262:516–531CrossRefGoogle Scholar
  8. 8.
    Favero J (1994) Lectins in AIDS research. Glycobiology 4:387–396CrossRefGoogle Scholar
  9. 9.
    Ji X, Gewurz H, Spear GT (2005) Mannose binding lectin (MBL) and HIV. Mol Immunol 42:145–152CrossRefGoogle Scholar
  10. 10.
    Balzarini J, Schols D, Neyts J, van Damme EJ, Peumans W, de Clercq E (1991) Alpha-(1–3)- and alpha-(1–6)-D-mannose-specific plant lectins are markedly inhibitory to human immunodeficiency virus and cytomegalovirus infections in vitro. Antimicrob Agents Chemother 35:410–416Google Scholar
  11. 11.
    Leonard CK, Spellman MW, Riddle L, Harris RJ, Thomas JN, Gregory TJ (1990) Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells. J Biol Chem 265:10373–10382Google Scholar
  12. 12.
    Hart ML, Saifuddin M, Uemura K, Bremer EG, Hooker B, Kawasaki T, Spear GT (2002) High mannose glycans and sialic acid on gp120 regulate binding of mannose-binding lectin (MBL) to HIV type 1. AIDS Res Hum Retroviruses 18:1311–1317CrossRefGoogle Scholar
  13. 13.
    Liu FF, Dong XY, Sun Y (2008) Molecular mechanism for the effects of trehalose on beta-hairpin folding revealed by molecular dynamics simulation. J Mol Graph Model 27:421–429CrossRefGoogle Scholar
  14. 14.
    Kundu S, Roy D (2008) Temperature-induced unfolding pathway of a type III antifreeze protein: insight from molecular dynamics simulation. J Mol Graph Model 27:88–94CrossRefGoogle Scholar
  15. 15.
    Jorgensen WL, C C, Madura JD (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79:926–935CrossRefGoogle Scholar
  16. 16.
    Case DA, Cheatham TE 3rd, Darden T, Gohlke H, Luo R, Merz KM, Onufriev A, Simmerling C, Wang B, Woods RJ (2005) The Amber biomolecular simulation programs. J Comput Chem 26:1668–1688CrossRefGoogle Scholar
  17. 17.
    Wang JM, Cieplak P, Kollman PA (2000) How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? J Comput Chem 21:1049–1074CrossRefGoogle Scholar
  18. 18.
    Kirschner KN, Woods RJ (2001) Solvent interactions determine carbohydrate conformation. Proc Natl Acad Sci USA 98:10541–10545CrossRefGoogle Scholar
  19. 19.
  20. 20.
    Larini L, Mannella R, Leporini D (2007) Langevin stabilization of molecular-dynamics simulations of polymers by means of quasisymplectic algorithms. J Chem Phys 126:104101CrossRefGoogle Scholar
  21. 21.
    Humphrey W, Dalke A, Schulten K (1996) VMD: visual molecular dynamics. J Mol Graph 14:33–38CrossRefGoogle Scholar
  22. 22.
    Guex N, Peitsch MC (1997) SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18:2714–2723CrossRefGoogle Scholar
  23. 23.
    Kollman PA, Massova I, Reyes C, Kuhn B, Huo S, Chong L, Lee M, Lee T, Duan Y, Wang W, Donini O, Cieplak P, Srinivasan J, Case DA, Cheatham TE 3rd (2000) Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc Chem Res 33:889–897CrossRefGoogle Scholar
  24. 24.
    Luo R, David L, Gilson MK (2002) Accelerated Poisson-Boltzmann calculations for static and dynamic systems. J Comput Chem 23:1244–1253CrossRefGoogle Scholar
  25. 25.
    Li T, Froeyen M, Herdewijn P (2008) Computational alanine scanning and free energy decomposition for E. coli type I signal peptidase with lipopeptide inhibitor complex. J Mol Graph Model 26:813–823CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Sichuan Key Laboratory of Molecular Biology and Biotechnology, Key Laboratory of Bio-resources and Eco-environment, Ministry of EducationCollege of Life Science, Sichuan UniversityChengduPeople’s Republic of China

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