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A New Flexible Protocol for Docking Studies

  • Lucia SessaEmail author
  • Luigi Di Biasi
  • Simona Concilio
  • Giuseppe Cattaneo
  • Alfredo De Santis
  • Pio Iannelli
  • Stefano Piotto
Conference paper
Part of the Communications in Computer and Information Science book series (CCIS, volume 587)

Abstract

A significant prerequisite for computational structure-based drug design is the estimation of the structures of ligand-receptor complexes. For this task, the flexibility of both ligand and receptor backbone is required, but it requires the exploration of an extremely vast conformational space. Here we present a protocol to address the receptor flexibility using complementary strategies and the use of receptor sequence conservation. The method aims to increase the accuracy of predicted ligand orientation in the binding pocket and the receptor-ligand binding affinity. The precision in affinity prediction permits to distinguish between binders and non-binders and to identify binding sites and ligand poses necessary for lead optimization.

Keywords

Androgen Receptor Binding Pocket Root Mean Square Deviation Internal Cavity Receptor Structure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was partially supported by the “Data-Driven Genomic Computing (GenData 2020)” PRIN project (2013–2015), funded by the Italian Ministry of the University and Research (MIUR).

References

  1. 1.
    Goldsmith, M.-R., Grulke, C.M., Chang, D.T., Transue, T.R., Little, S.B., Rabinowitz, J.R., Tornero-Velez, R.: DockScreen: A Database of In Silico Biomolecular Interactions to Support Computational Toxicology. Dataset Papers in Science 2014 (2014)Google Scholar
  2. 2.
    Pomerantz, M.M., Li, F., Takeda, D.Y., Lenci, R., Chonkar, A., Chabot, M., Cejas, P., Vazquez, F., Cook, J., Shivdasani, R.A., Bowden, M., Lis, R., Hahn, W.C., Kantoff, P.W., Brown, M., Loda, M., Long, H.W., Freedman, M.L.: The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis. Nat. Genet. 47(11), 1346–1351 (2015)CrossRefGoogle Scholar
  3. 3.
    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), e72052 (2013)CrossRefGoogle Scholar
  4. 4.
    Piotto, S., Concilio, S., Bianchino, E., Iannelli, P., López, D.J., Terés, S., Ibarguren, M., Barceló-Coblijn, G., Martin, M.L., Guardiola-Serrano, F.: Differential effect of 2-hydroxyoleic acid enantiomers on protein (sphingomyelin synthase) and lipid (membrane) targets. Biochim. Biophys. Acta (BBA)-Biomembr. 1838(6), 1628–1637 (2014)CrossRefGoogle Scholar
  5. 5.
    Piotto, S., Concilio, S., Mavelli, F., Iannelli, P.: Computer simulations of natural and synthetic polymers in confined systems. Macromolecular symposia 286(1), 25–33 (2009)CrossRefGoogle Scholar
  6. 6.
    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. Biophys. Acta (BBA)- Biomembr. 1838(6), 1509–1517 (2014)CrossRefGoogle Scholar
  7. 7.
    Piotto, S.P., Sessa, L., Concilio, S., Iannelli, P.: YADAMP: yet another database of antimicrobial peptides. Int. J. Antimicrob. Agents 39(4), 346–351 (2012)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. Biophys. Acta (BBA)- Biomembr. 1838(3), 1010–1018 (2014)CrossRefGoogle Scholar
  9. 9.
    Piotto, S., Nesper, R.: CURVIS: A program to study and analyse crystallographic structures and phase transitions. J. Appl. Crystallogr. 38(1), 223–227 (2005)CrossRefGoogle Scholar
  10. 10.
    Torok, Z., Crul, T., Maresca, B., Schutz, G.J., Viana, F., Dindia, L., Piotto, S., Brameshuber, M., Balogh, G., Peter, M., Porta, A., Trapani, A., Gombos, I., Glatz, A., Gungor, B., Peksel, B., Vigh Jr., L., Csoboz, B., Horvath, I., Vijayan, M.M., Hooper, P.L., Harwood, J.L., Vigh, L.: Plasma membranes as heat stress sensors: from lipid-controlled molecular switches to therapeutic applications. Biochim. Biophys. Acta 1838(6), 1594–1618 (2014)CrossRefGoogle Scholar
  11. 11.
    Crul, T., Toth, N., Piotto, S., Literati-Nagy, P., Tory, K., Haldimann, P., Kalmar, B., Greensmith, L., Torok, Z., Balogh, G., Gombos, I., Campana, F., Concilio, S., Gallyas, F., Nagy, G., Berente, Z., Gungor, B., Peter, M., Glatz, A., Hunya, A., Literati-Nagy, Z., Vigh Jr., L., Hoogstra-Berends, F., Heeres, A., Kuipers, I., Loen, L., Seerden, J.P., Zhang, D., Meijering, R.A., Henning, R.H., Brundel, B.J., Kampinga, H.H., Koranyi, L., Szilvassy, Z., Mandl, J., Sumegi, B., Febbraio, M.A., Horvath, I., Hooper, P.L., Vigh, L.: Hydroximic acid derivatives: pleiotropic HSP co-inducers restoring homeostasis and robustness. Curr. Pharm. Des. 19(3), 309–346 (2013)CrossRefGoogle Scholar
  12. 12.
    Gombos, I., Crul, T., Piotto, S., Gungor, B., Torok, Z., Balogh, G., Peter, M., Slotte, J.P., Campana, F., Pilbat, A.M., Hunya, A., Toth, N., Literati-Nagy, Z., Vigh Jr., L., Glatz, A., Brameshuber, M., Schutz, G.J., Hevener, A., Febbraio, M.A., Horvath, I., Vigh, L.: Membrane-lipid therapy in operation: the HSP co-inducer BGP-15 activates stress signal transduction pathways by remodeling plasma membrane rafts. PLoS ONE 6(12), e28818 (2011)CrossRefGoogle Scholar
  13. 13.
    Vigh, L., Torok, Z., Balogh, G., Glatz, A., Piotto, S., Horvath, I.: Membrane-regulated stress response: a theoretical and practical approach. In: Vigh, L., Csermely, L. (eds.) Molecular Aspects of the Stress Response: Chaperones, Membranes and Networks. Advances in experimental medicine and biology, vol. 594, pp. 114–131. Springer Science + Business Media, New York (2007)CrossRefGoogle Scholar
  14. 14.
    Lange, O.F., Lakomek, N.-A., Farès, C., Schröder, G.F., Glatz, A., Walter, K.F., Becker, S., Meiler, J., Grubmüller, H., Griesinger, C., De Groot, B.L.: Recognition dynamics up to microseconds revealed from an RDC-derived ubiquitin ensemble in solution. Science 320(5882), 1471–1475 (2008)CrossRefGoogle Scholar
  15. 15.
    Mittermaier, A., Kay, L.E.: New tools provide new insights in NMR studies of protein dynamics. Science 312(5771), 224–228 (2006)CrossRefGoogle Scholar
  16. 16.
    Tuffery, P., Derreumaux, P.: Flexibility and binding affinity in protein–ligand, protein–protein and multi-component protein interactions: limitations of current computational approaches. J. Roy. Soc. Interface 9(66), 20–33 (2012)CrossRefGoogle Scholar
  17. 17.
    Chou, K.C.: Biological functions of low-frequency vibrations (phonons). III. Helical structures and microenvironment. Biophys. J. 45(5), 881–889 (1984)CrossRefGoogle Scholar
  18. 18.
    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
  19. 19.
    Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T., Weissig, H., Shindyalov, I.N., Bourne, P.E.: The protein data bank. Nucleic Acids Res. 28(1), 235–242 (2000)CrossRefGoogle Scholar
  20. 20.
    Krieger, E., Vriend, G.: YASARA View - molecular graphics for all devices - from smartphones to workstations. Bioinformatics 30(20), 2981–2982 (2014)CrossRefGoogle Scholar
  21. 21.
    Trott, O., Olson, A.J.: 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

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Lucia Sessa
    • 1
    Email author
  • Luigi Di Biasi
    • 1
    • 2
  • Simona Concilio
    • 3
  • Giuseppe Cattaneo
    • 2
  • Alfredo De Santis
    • 2
  • Pio Iannelli
    • 1
  • Stefano Piotto
    • 1
  1. 1.Department of PharmacyUniversity of SalernoFiscianoItaly
  2. 2.Department of InformaticsUniversity of SalernoFiscianoItaly
  3. 3.Department of Industrial EngineeringUniversity of SalernoFiscianoItaly

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