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VSDMIP 1.5: an automated structure- and ligand-based virtual screening platform with a PyMOL graphical user interface

  • Álvaro Cortés Cabrera
  • Rubén Gil-Redondo
  • Almudena Perona
  • Federico Gago
  • Antonio MorrealeEmail author
Article

Abstract

A graphical user interface (GUI) for our previously published virtual screening (VS) and data management platform VSDMIP (Gil-Redondo et al. J Comput Aided Mol Design, 23:171–184, 2009) that has been developed as a plugin for the popular molecular visualization program PyMOL is presented. In addition, a ligand-based VS module (LBVS) has been implemented that complements the already existing structure-based VS (SBVS) module and can be used in those cases where the receptor’s 3D structure is not known or for pre-filtering purposes. This updated version of VSDMIP is placed in the context of similar available software and its LBVS and SBVS capabilities are tested here on a reduced set of the Directory of Useful Decoys database. Comparison of results from both approaches confirms the trend found in previous studies that LBVS outperforms SBVS. We also show that by combining LBVS and SBVS, and using a cluster of ~100 modern processors, it is possible to perform complete VS studies of several million molecules in less than a month. As the main processes in VSDMIP are 100% scalable, more powerful processors and larger clusters would notably decrease this time span. The plugin is distributed under an academic license upon request from the authors.

Keywords

Docking Virtual screening Drug design Graphical user interface 

Notes

Acknowledgments

The authors thank Dr. Eva Mª Priego and Dr. Alberto Gómez for testing the application and valuable comments, as well as the rest of members of the Bioinformatics Unit at CBMSO and the Molecular Modeling group at UAH for encouragement and fruitful discussions. This work was supported by grants from Ministerio de Ciencia e Innovación (MICINN) BIO2008-04384 (to A. M.) and SAF2009-13914-C02-02 (to F. G.), and Comunidad Autónoma de Madrid (CAM) S-BIO-0214-2006. A. M. acknowledges CAM for financial support through the AMAROUTO program to the Fundación Severo Ochoa, R. G. -R. thanks MICINN for a contract from “Programa de Personal Técnico y de Apoyo 2008”, and A. C. thanks Ministerio de Educación for the FPU grant AP2009-0203. We are grateful to OpenEye Scientific Software, Inc. for providing us with an academic license for their software. The technical support and advice from the Bioinformatics Facility at CBMSO is gratefully acknowledged, as well as the computer resources, technical expertise and assistance provided by the Barcelona Supercomputing Center—Centro Nacional de Supercomputación.

References

  1. 1.
    Munos B (2009) Nat Rev Drug Discov 8(12):959CrossRefGoogle Scholar
  2. 2.
    Jorgensen WL (2004) Science 303(5665):1813CrossRefGoogle Scholar
  3. 3.
    Zhou HX, Gilson MK (2009) Chem Rev 109(9):4092CrossRefGoogle Scholar
  4. 4.
    Ivanov AS, Veselovsky AV, Dubanov AV, Skvortsov VS (2006) Methods Mol Biol 316:389Google Scholar
  5. 5.
    Maestro (2011) Maestro, version 9.2. Schrödinger, LLC, New YorkGoogle Scholar
  6. 6.
    SYBYL-X 1.2. (2011) Tripos International, 1699 South Hanley Rd., St. Louis, Missouri, 63144, USAGoogle Scholar
  7. 7.
    Schulz T, Pleiss J, Schmid R (2000) Protein Sci 9(6):1053CrossRefGoogle Scholar
  8. 8.
    Hassan M, Brown RD, Varma-O’brien S, Rogers D (2006) Mol Divers 10(3):283CrossRefGoogle Scholar
  9. 9.
    DeLano WL (2002) The PyMOL molecular graphics system. Schrodinger Inc, New YorkGoogle Scholar
  10. 10.
    Seeliger D, de Groot BL (2010) J Comput Aided Mol Des 24(5):417CrossRefGoogle Scholar
  11. 11.
    Lill MA, Danielson ML (2011) J Comput Aided Mol Des 25(1):13CrossRefGoogle Scholar
  12. 12.
    Irwin JJ, Shoichet BK, Mysinger MM, Huang N, Colizzi F, Wassam P, Cao Y (2009) J Med Chem 52(18):5712CrossRefGoogle Scholar
  13. 13.
    Beautrait A, Leroux V, Chavent M, Ghemtio L, Devignes MD, Smail-Tabbone M, Cai W, Shao X, Moreau G, Bladon P, Yao J, Maigret B (2008) J Mol Model 14(2):135CrossRefGoogle Scholar
  14. 14.
    Zhou T, Caflisch A (2009) J Chem Inf Model 49(1):145CrossRefGoogle Scholar
  15. 15.
    Gil-Redondo R, Estrada J, Morreale A, Herranz F, Sancho J, Ortiz AR (2009) J Comput Aided Mol Des 23(3):171CrossRefGoogle Scholar
  16. 16.
    Huang N, Shoichet BK, Irwin JJ (2006) J Med Chem 49(23):6789CrossRefGoogle Scholar
  17. 17.
    Murray CW, Baxter CA, Frenkel AD (1999) J Comput Aided Mol Des 13(6):547CrossRefGoogle Scholar
  18. 18.
    Schneider G, Neidhart W, Giller T, Schmid G (1999) Angew Chem Int Ed 38(19):2894CrossRefGoogle Scholar
  19. 19.
    Open Babel: The open source chemistry toolbox; 2011Google Scholar
  20. 20.
    Weininger D (1988) J Chem Inf Comput Sci 28(1):31CrossRefGoogle Scholar
  21. 21.
    Case DA, Cheatham TE III, Darden T, Gohlke H, Luo R, Merz KM Jr, Onufriev A, Simmerling C, Wang B, Woods RJ (2005) J Comput Chem 26(16):1668CrossRefGoogle Scholar
  22. 22.
    Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML (1983) J Chem Phys 79:926CrossRefGoogle Scholar
  23. 23.
    Zacharias M, Luty BA, Davis ME, McCammon JA (1994) J Mol Biol 238(3):455CrossRefGoogle Scholar
  24. 24.
    Pastor M, Cruciani G (1995) J Med Chem 38(23):4637CrossRefGoogle Scholar
  25. 25.
    Perez C, Ortiz AR (2001) J Med Chem 44(23):3768CrossRefGoogle Scholar
  26. 26.
    Weininger D (1988) J Chem Inf Model 28(1):31CrossRefGoogle Scholar
  27. 27.
    Corina. Computerchemie Langemarckplatz 1, Erlangen, Germany: Molecular Networks GmbH; 2000Google Scholar
  28. 28.
    Stewart JJ (1990) J Comput Aided Mol Des 4(1):1CrossRefGoogle Scholar
  29. 29.
    Gil Redondo R (2006). Master thesis. UNED, MadridGoogle Scholar
  30. 30.
    Dolinsky TJ, Nielsen JE, McCammon JA, Baker NA (2004) Nucleic Acids Res 32(suppl 2):W665CrossRefGoogle Scholar
  31. 31.
    Li H, Robertson AD, Jensen JH (2005) Protein Struct Funct Bioinforma 61(4):704CrossRefGoogle Scholar
  32. 32.
    Triballeau N, Acher F, Brabet I, Pin JP, Bertrand HO (2005) J Med Chem 48(7):2534CrossRefGoogle Scholar
  33. 33.
    Guha R, Howard MT, Hutchison GR, Murray-Rust P, Rzepa H, Steinbeck C, Wegner J, Egon L, Willighagen O (2006) J chem inf model 46(3):991CrossRefGoogle Scholar
  34. 34.
    MySQL++. A MySQL API for C++: TangensoftGoogle Scholar
  35. 35.
    Watson P, Verdonk M, Hartshorn MJ (2003) J Mol Graph Model 22(1):71CrossRefGoogle Scholar
  36. 36.
    Lehtovuori PT, Nyronen TH (2006) J Chem Inf Model 46(2):620CrossRefGoogle Scholar
  37. 37.
    Preisach C, Burkhardt H, Schmidt-Thieme L, Decker R, Berthold MR, Cebron N, Dill F, Gabriel TR, Kötter T, Meinl T, Ohl P, Sieb C, Thiel K, Wiswedel B (2008) KNIME The Konstanz information miner. In: Bock HH, Gaul W, Schader M et al (eds) Data analysis. machine learning and applications. Springer, Berlin Heidelberg, p 319Google Scholar
  38. 38.
    Bak A, Polanski J, Kurczyk A (2009) Molecules 14(9):3436CrossRefGoogle Scholar
  39. 39.
    Sander T, Freyss J, von Korff M, Reich JR, Rufener C (2009) J Chem Inf Model 49(2):232–246Google Scholar
  40. 40.
    Brodney MD, Brosius AD, Gregory T, Heck SD, Klug-McLeod JL, Poss CS (2009) J Chem Inf Model 49(12):2639CrossRefGoogle Scholar
  41. 41.
    Vaque M, Arola A, Aliagas C, Pujadas G (2006) Bioinformatics 22(14):1803CrossRefGoogle Scholar
  42. 42.
    Zhang S, Kumar K, Jiang X, Wallqvist A, Reifman J (2008) BMC Bioinformatics 9:126CrossRefGoogle Scholar
  43. 43.
    Jiang X, Kumar K, Hu X, Wallqvist A, Reifman J (2008) Chem Cent J 2:18CrossRefGoogle Scholar
  44. 44.
    Prakhov ND, Chernorudskiy AL, Gainullin MR (2010) Bioinformatics 26(10):1374CrossRefGoogle Scholar
  45. 45.
    Pencheva T, Lagorce D, Pajeva I, Villoutreix BO, Miteva MA (2008) BMC Bioinformatics 9:438CrossRefGoogle Scholar
  46. 46.
    Hsu KC, Chen YF, Lin SR, Yang JM (2011) BMC Bioinformatics 12(Suppl 1):S33CrossRefGoogle Scholar
  47. 47.
    Modest von Korff JF, Sander Thomas (2009) J Chem Inf Model 49(2):209CrossRefGoogle Scholar
  48. 48.
    Cross JB, Thompson DC, Rai BK, Baber JC, Fan KY, Hu Y, Humblet C (2009) J Chem Inf Model 49(6):1455CrossRefGoogle Scholar
  49. 49.
    Verdonk ML, Berdini V, Hartshorn MJ, Mooij WT, Murray CW, Taylor RD, Watson P (2004) J Chem Inf Comput Sci 44(3):793CrossRefGoogle Scholar
  50. 50.
    Irwin JJ (2008) J Comput Aided Mol Des 22(3–4):193CrossRefGoogle Scholar
  51. 51.
    Venkatraman V, Perez-Nueno VI, Mavridis L, Ritchie DW (2010) J Chem Inf Model 50(12):2079CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Álvaro Cortés Cabrera
    • 1
    • 2
  • Rubén Gil-Redondo
    • 2
  • Almudena Perona
    • 2
  • Federico Gago
    • 1
  • Antonio Morreale
    • 2
    Email author
  1. 1.Departamento de FarmacologíaUniversidad de AlcaláAlcalá de Henares, MadridSpain
  2. 2.Unidad de BioinformáticaCentro de Biología Molecular Severo Ochoa (CSIC-UAM)MadridSpain

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