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Molecular Dynamics and Morphing Protocols for High Accuracy Molecular Docking

  • Lucia SessaEmail author
  • Simona Concilio
  • Stefano Piotto
Chapter
Part of the Lecture Notes in Bioengineering book series (LNBE)

Abstract

Molecular docking is a popular technique to analyse the geometry and the interactions of a ligand in a protein binding site. Flexibility in molecular docking studies is particularly important when the binding pocket is buried inside the protein and the ligand binding is responsible for backbone deformation of the receptor. The major limit is that the most popular docking programs do not consider the conformation changes in the protein of the receptor during the process of binding of the ligand. Here we have considered sampling of molecular dynamics trajectory, and morphing protocol to generate conformers of the receptor, which differs from the available crystal structure. We have also considered the presence of conserved residues to drive ligands toward the binding pocket under blind docking analysis.

Keywords

Flexible docking Yada Cross-docking 

References

  1. 1.
    Zhao, H., Dong, J., Lafleur, K., Nevado, C., Caflisch, A.: Discovery of a novel chemotype of tyrosine kinase inhibitors by fragment-based docking and molecular dynamics. ACS Med. Chem. Lett. 3(10), 834–838 (2012)CrossRefGoogle Scholar
  2. 2.
    de Ruyck, J., Brysbaert, G., Blossey, R., Lensink, M.F.: Molecular docking as a popular tool in drug design, an in silico travel. Adv. Appl. Bioinform. Chem. AABC 9, (1–11) (2016)Google Scholar
  3. 3.
    Meng, X.-Y., Zhang, H.-X., Mezei, M., Cui, M.: Molecular docking: a powerful approach for structure-based drug discovery. Curr. Comput. Aided Drug Des. 7(2), 146–157 (2011)CrossRefGoogle Scholar
  4. 4.
    Piotto, S., Di Biasi, L., Fino, R., Parisi, R., Sessa, L., Concilio, S.: Yada: a novel tool for molecular docking calculations. J. Comput. Aided Mol. Des. 30(9), 753–759 (2016)CrossRefGoogle Scholar
  5. 5.
    Lopez, D.H., Fiol-deRoque, M.A., Noguera-Salvà, M.A., Terés, S., Campana, F., Piotto, S., Castro, J.A., Mohaibes, R.J., Escribá, P.V., Busquets, X.: 2-Hydroxy arachidonic acid: a new non-steroidal anti-inflammatory drug. PLoS ONE 8(8) (2013)Google Scholar
  6. 6.
    Piotto, S., Concilio, S., Bianchino, E., Iannelli, P., López, D.J., Terés, S., Ibarguren, M., Barceló-Coblijn, G., Martin, M.L., Guardiola-Serrano, F., Alonso-Sande, M., Funari, S.S., Busquets, X., Escribá, P.V.: Differential effect of 2-hydroxyoleic acid enantiomers on protein (sphingomyelin synthase) and lipid (membrane) targets. Biochim. et Biophys. Acta—Biomembr. 1838(6), 1628–1637 (2014)CrossRefGoogle Scholar
  7. 7.
    Piotto, S., Trapani, A., Bianchino, E., Ibarguren, M., López, D.J., Busquets, X., Concilio, S.: The effect of hydroxylated fatty acid-containing phospholipids in the remodeling of lipid membranes. Biochim. et Biophys. Acta—Biomembr. 1838(6), 1509–1517 (2014)CrossRefGoogle Scholar
  8. 8.
    Scrima, M., Di Marino, S., Grimaldi, M., Campana, F., Vitiello, G., Piotto, S.P., D’Errico, G., D’Ursi, A.M.: Structural features of the C8 antiviral peptide in a membrane-mimicking environment. Biochim. et Biophys. Acta—Biomembr. 1838(3), 1010–1018 (2014)CrossRefGoogle Scholar
  9. 9.
    Zhao, H., Caflisch, A.: Molecular dynamics in drug design. European journal of medicinal chemistry 91(4–14 (2015)Google Scholar
  10. 10.
    Di Biasi, L., Fino, R., Parisi, R., Sessa, L., Cattaneo, G., De Santis, A., Iannelli, P., Piotto, S.: Novel algorithm for efficient distribution of molecular docking calculations. Commun. Comput. Inf. Sci. 587, 65–74 (2016)Google Scholar
  11. 11.
    Tan, M.H.E., Li, J., Xu, H.E., Melcher, K.: Yong, E.-l.: Androgen receptor: structure, role in prostate cancer and drug discovery. Acta Pharmacol. Sin. 36(1), 3–23 (2015)CrossRefGoogle Scholar
  12. 12.
    Ferraldeschi, R., Welti, J., Luo, J., Attard, G., de Bono, J.S.: Targeting the androgen receptor pathway in castration-resistant prostate cancer: progresses and prospects. Oncogene 34(14), 1745–1757 (2015)CrossRefGoogle Scholar
  13. 13.
    Krieger, E., Vriend, G.: YASARA View—molecular graphics for all devices—from smartphones to workstations. Bioinformatics 30(20), 2981–2982 (2014)CrossRefGoogle Scholar
  14. 14.
    Case, D.A., Babin, V., Berryman, J., Betz, R., Cai, Q., Cerutti, D., Cheatham Iii, T., Darden, T., Duke, R., Gohlke, H.: Amber 14 (2014)Google Scholar
  15. 15.
    Piotto, S., Di Biasi, L., Fino, R., Parisi, R., Sessa, L.: Yada: a novel tool for molecular docking calculations. J. Comput. Aided Mol. Des. 30(9), 753–759 (2016)CrossRefGoogle Scholar
  16. 16.
    Piotto, S., Biasi, L.D., Concilio, S., Castiglione, A., Cattaneo, G.: GRIMD: distributed computing for chemists and biologists. Bioinformation 10(1), 43–47 (2014)CrossRefGoogle Scholar
  17. 17.
    Johnson, M., Zaretskaya, I., Raytselis, Y., Merezhuk, Y., McGinnis, S., Madden, T.L.: NCBI BLAST: a better web interface. Nucleic Acids Res. 36(Web Server issue), W5–9 (2008)Google Scholar
  18. 18.
    UniProt, C.: UniProt: a hub for protein information. Nucleic Acids Res. 43(Database issue), D204–212 (2015)Google Scholar
  19. 19.
    McWilliam, H., Li, W., Uludag, M., Squizzato, S., Park, Y.M., Buso, N., Cowley, A.P., Lopez, R.: Analysis Tool Web Services from the EMBL-EBI. Nucleic Acids Res. 41(Web Server issue), W597–600 (2013)Google Scholar
  20. 20.
    Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S., Olson, A.J.: AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J. Comput. Chem. 30(16), 2785–2791 (2009)CrossRefGoogle Scholar
  21. 21.
    Trott, O., Olson, A.J.: Software news and update AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31(2), 455–461 (2010)Google Scholar
  22. 22.
    Friesner, R.A., Banks, J.L., Murphy, R.B., Halgren, T.A., Klicic, J.J., Mainz, D.T., Repasky, M.P., Knoll, E.H., Shelley, M., Perry, J.K., Shaw, D.E., Francis, P., Shenkin, P.S.: Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem. 47(7), 1739–1749 (2004)CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of PharmacyUniversity of SalernoFiscianoItaly
  2. 2.Department of Industrial EngineeringUniversity of SalernoFiscianoItaly

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