Advertisement

Molecular Biology

, Volume 50, Issue 2, pp 313–319 | Cite as

Binding of 1-substituted carbazolyl-3,4-dihydro-β-carbolines with DNA: Molecular dynamics simulation and MM-GBSA analysis

  • M. SargolzaeiEmail author
  • M. Afshar
  • M. N. Jorabchi
Structural and Functional Analysis of Biopolymers and Biopolymer Complexes
  • 47 Downloads

Abstract

Molecular Mechanics-Generalized Born-Solvent Accessibility free energy calculations were used to analyse DNA binding affinity of 1-substituted carbazolyl-3,4-dihydro-β-carboline molecules. In this study, DNA structure with sequence of d(CGATCG)2 was used for simulations. 15 ns molecular dynamics simulations of the studied complexes were performed. The calculated free energy was compared with experimental antitumor activity (IC50). The predicted free energies decreased with the increase of IC50 values. It was shown that molecules 1–6 bind to DNA via intercalation mode, while molecules 7–9 bind through groove binding mode. Also, it was found that the vdW energy term (ΔE vdW) and the non-polar desolvation energy (ΔG SA) are the favorable terms for binding energy, whereas net electrostatic energies (ΔE ele + ΔG GB) and conformational entropy energy (TΔS) are unfavorable ones.

Keywords

anticancer drug binding affinity Gibbs free energy alkaloid 

Abbreviations

MM-GBSA

Molecular Mechanics-Generalized Born-Solvent Accessibility

MM-PBSA

Molecular Mechanics-Molecular mechanics-Poisson Boltzmann Surface Area

FEP

Free Energy Perturbation

TI

Thermodynamic Integration

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Schupp P., Proksch P., Wray V. 2002. Further new staurosporine derivatives from the ascidian Eudistoma toealensis and its predatory flatworm Pseudoceros sp. J. Nat. Prod. 65, 295–298.CrossRefPubMedGoogle Scholar
  2. 2.
    Schupp P., Poehner T., Edrada R., Ebel R., Berg A., Wray V., Proksch P. 2003. Eudistomins W and X, two new β-carbolines from the Micronesian tunicate Eudistoma sp. J. Nat. Prod. 66, 272–275.CrossRefPubMedGoogle Scholar
  3. 3.
    Prinsep M.R., Blunt J.W., Munro M.H.G. 1991. New cytotoxic β-carboline alkaloids from the marine bryozoan, Cribricellina cribraria. J. Nat. Prod. 54, 1068–1076.CrossRefPubMedGoogle Scholar
  4. 4.
    Harwood D.T., Urban S., Blunt J.W., Munro M.H.G. 2003. β-Carboline alkaloids from a New Zealand marine bryozoan, Cribricellina cribraria. Nat. Prod. Res. 17, 15–19.CrossRefPubMedGoogle Scholar
  5. 5.
    Beutler J.A., Cardellina J.H., Prather T., Shoemaker R.H., Boyd M.R., Snader K.M. 1993. A cytotoxic β-carboline from the bryozoan Catenicella cribraria. J. Nat. Prod. 56, 1825–1826.CrossRefPubMedGoogle Scholar
  6. 6.
    Peng J., Shen X., El Sayed K.A., Dunbar D.C., Perry T.L., Wilkins S.P., Hamann M.T., Bobzin S., Huesing J., Camp R., Prinsen M., Krupa D., Wideman M.A. 2003. Marine natural products as prototype agrochemical agents. J. Agric. Food Chem. 51, 2246–2252.CrossRefPubMedGoogle Scholar
  7. 7.
    Edrada R.A., Proksch P., Wray V., Witte L., Müller W.E.G., van Soest R.W.M. 1996. Four new bioactive manzamine type alkaloids from the Philippine marine sponge Xestospongia ashmorica. J. Nat. Prod. 59, 1056–1060.CrossRefPubMedGoogle Scholar
  8. 8.
    Sakai R., Higa T., Jefford C.W., Bernardinelli G. 1986. Manzamine A, a novel antitumor alkaloid from a sponge. J. Am. Chem. Soc. 108, 6404–6405.CrossRefGoogle Scholar
  9. 9.
    Nakamura H., Deng S., Kobayashi Ji, Ohizumi Y., Tomotake Y., Matsuzaki T., Hirata Y. 1987. Keramamine-A and -B, novel antimicrobial alkaloids from the Okinawan marine sponge Pellina sp. Tetrahedron Lett. 28, 621–624.CrossRefGoogle Scholar
  10. 10.
    Higa T., Sakai R., Ichiba T. 1990. US Patent 4895852.Google Scholar
  11. 11.
    Higa T., Sakai R., Kohmoto S., Lui M.S. 1990. US Patent 4895853.Google Scholar
  12. 12.
    Higa T., Sakai R. 1990. US Patent 4895854.Google Scholar
  13. 13.
    Rao K.V., Santarsiero B.D., Mesecar A.D., Schinazi R.F., Tekwani B.L., Hamann M.T. 2003. New manzamine alkaloids with activity against infectious and tropical parasitic diseases from an Indonesian sponge. J. Nat. Prod. 66, 823–828.CrossRefPubMedGoogle Scholar
  14. 14.
    Shen Y.C., Chang Y.T., Lin C.L., Liaw C.C., Kuo Y.H., Tu L.C., Chern J.W. 2011. Synthesis of 1-substituted carbazolyl-1,2,3,4-tetrahydro-and carbazolyl-3,4-dihydro-β-carboline analogs as potential antitumor agents. Marine Drugs. 9, 256—277.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Yousaf M., Sayed K.I., Rao K.V. et al. 2002. 12,34-Oxamanzamines, novel biocatalytic and natural products from manzamine-producing Indo-Pacific sponges. Tetrahedron. 58, 7397–7402.CrossRefGoogle Scholar
  16. 16.
    Liu M., Yuan M., Luo M., Bu X., Luo H.-B., Hu X. 2010. Binding of curcumin with glyoxalase I: Molecular docking, molecular dynamics simulations, and kinetics analysis. Biophys. Chem. 147, 28–34.CrossRefPubMedGoogle Scholar
  17. 17.
    Adekoya O.A., Willassen N.-P., Sylte I. 2006. Molecular insight into pseudolysin inhibition using the MM-PBSA and LIE methods. J. Struct. Biol. 153, 129–144.CrossRefPubMedGoogle Scholar
  18. 18.
    Shaikh S.A., Ahmed S.R., Jayaram B. 2004. A molecular thermodynamic view of DNA drug interactions: A case study of 25 minor-groove binders. Arch. Biochem. Biophys. 429, 81–99.CrossRefPubMedGoogle Scholar
  19. 19.
    Hou T., Wang J., Li Y., Wang W. 2010. Assessing the performance of the MM/PBSA and MM/GBSA methods: 1. The accuracy of binding free energy calculations based on molecular dynamics simulations. J. Chem. Inform. Model. 51, 69–82.CrossRefGoogle Scholar
  20. 20.
    Becke A.D. 1993. Density-functional thermochemistry: 3. The role of exact exchange. J. Chem. Physics. 98, 5648–5652.CrossRefGoogle Scholar
  21. 21.
    Frisch M.J., Trucks G.W., Schlegel H.B., et al. 2004. Gaussian 03, Revision C.02. Wallingford, CT.: Gaussian, Inc.Google Scholar
  22. 22.
    Sanner M.F., Olson A.J., Spehner J.C. 1996. Reduced surface: An efficient way to compute molecular surfaces. Biopolymers. 38, 305–320.CrossRefPubMedGoogle Scholar
  23. 23.
    Bayly C.I., Cieplak P., Cornell W., Kollman P.A. 1993. A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: The RESP model. J. Phys. Chem. 97, 10269–10280.CrossRefGoogle Scholar
  24. 24.
    Thompson, M.A., ArgusLab 4.0.1 Software, Seattle, WA: Planaria Software LLC. http://www.arguslab.com/Google Scholar
  25. 25.
    Case D.A., Cheatham T.E., Darden T., Gohlke H., Luo R., Merz K.M., Onufriev A., Simmerling C., Wang B., Woods R.J. 2005. The Amber biomolecular simulation programs. J. Comput. Chem. 26, 1668–1688.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Cheatham T.E., 3rd, Cieplak P., Kollman P.A. 1999. A modified version of the Cornell et al. force field with improved sugar pucker phases and helical repeat. J. Biomol. Struct. Dyn. 16, 845–862.CrossRefPubMedGoogle Scholar
  27. 27.
    Pérez A., Marchán I., Svozil D., Sponer J., Cheatham T.E., 3rd, Laughton C.A., Orozco M. 2007. Refinement of the AMBER force field for nucleic acids: Improving the description of α/γ conformers. Biophys. J. 92, 3817–3829.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Wang J., Wolf R.M., Caldwell J.W., Kollman P.A., Case D.A. 2004. Development and testing of general amber force field. J. Comput. Chem. 25, 1157–1174.CrossRefPubMedGoogle Scholar
  29. 29.
    Berendsen H.J.C., Postma J.P.M., Gunsteren W.F., Hermans J. 1981. Interaction models for water in relation to protein hydration. In: Intermolecular Forces, vol. 14. Ed. Pullman B. Dordrecht: D. Reidel Publ., pp. 331–342.CrossRefGoogle Scholar
  30. 30.
    Ryckaert J.-P., Ciccotti G., Berendsen H.J.C. 1977. Numerical integration of the Cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. J. Comput. Phys. 23, 327–341.CrossRefGoogle Scholar
  31. 31.
    Parisi Ga., Wu Y.-S. 1981. Perturbation theory without gauge fixing. Sci. Sin. 24, 483–512.Google Scholar
  32. 32.
    Kollman P.A., 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 D.A., Cheatham T.E. 3rd. 2000. Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models. Acc. Chem. Res. 33, 889–897.CrossRefPubMedGoogle Scholar
  33. 33.
    Wang J., Hou T., Xu X. 2006. Recent advances in free energy calculations with a combination of molecular mechanics and continuum models. Curr. Comp. Aided Drug Design. 2, 287–306.CrossRefGoogle Scholar
  34. 34.
    Weiser J., Shenkin P.S., Still W.C. 1999. Approximate atomic surfaces from linear combinations of pairwise overlaps (LCPO). J. Comput. Chem. 20, 217–230.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2016

Authors and Affiliations

  1. 1.Department of ChemistryShahrood University of TechnologyShahroodIran
  2. 2.Materials Simulation Laboratory, Department of PhysicsIran University of Science and TechnologyNarmak, TehranIran
  3. 3.Physikalische und Theoretische ChemieInstitut für Chemie, Universität RostockRostockGermany

Personalised recommendations