Small-Molecule Library Screening by Docking with PyRx

  • Sargis DallakyanEmail author
  • Arthur J. Olson
Part of the Methods in Molecular Biology book series (MIMB, volume 1263)


Virtual molecular screening is used to dock small-molecule libraries to a macromolecule in order to find lead compounds with desired biological function. This in silico method is well known for its application in computer-aided drug design. This chapter describes how to perform small-molecule virtual screening by docking with PyRx, which is open-source software with an intuitive user interface that runs on all major operating systems (Linux, Windows, and Mac OS). Specific steps for using PyRx, as well as considerations for data preparation, docking, and data analysis, are also described.

Key words

Virtual molecular screening Computer-aided drug design Molecular docking PubChem AutoDock Vina Open Babel 



This work was supported by National Institute of Health (NIH) grant R01GM069832. The authors are very grateful to all those who contributed software used in this chapter. We also would like to thank Alex L. Perryman, Oleg Trott, Ruth Huey, and all members of our laboratories for helpful comments and discussions. This is manuscript # 25035 from The Scripps Research Institute.


  1. 1.
    Ng R (2008) Drugs: from discovery to approval, 2nd edn. Wiley-Blackwell, Hoboken, NJCrossRefGoogle Scholar
  2. 2.
    Swinney DC, Anthony J (2011) How were new medicines discovered? Nat Rev Drug Discov 10:507–519PubMedCrossRefGoogle Scholar
  3. 3.
    Jacob RB, Andersen T, McDougal OM (2012) Accessible high-throughput virtual screening molecular docking software for students and educators. PLoS Comput Biol 8:e1002499PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Lindell SD, Pattenden LC, Shannon J (2009) Combinatorial chemistry in the agrosciences. Bioorg Med Chem 17:4035–4046PubMedCrossRefGoogle Scholar
  5. 5.
    Varghese JN et al (1992) The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor. Proteins 14:327–332PubMedCrossRefGoogle Scholar
  6. 6.
    McKimm-Breschkin JL (2013) Influenza neuraminidase inhibitors: antiviral action and mechanisms of resistance. Influenza Other Respir Viruses 7:25–36PubMedCrossRefGoogle Scholar
  7. 7.
    Knox C et al (2011) DrugBank 3.0: a comprehensive resource for ‘omics’ research on drugs. Nucleic Acids Res 39:D1035–D1041PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Li Q et al (2010) PubChem as a public resource for drug discovery. Drug Discov Today 15:1052–1057PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Berman HM et al (2002) The protein data bank. Acta Crystallogr D Biol Crystallogr 58:899–907PubMedCrossRefGoogle Scholar
  10. 10.
    Scior T et al (2012) Recognizing pitfalls in virtual screening: a critical review. J Chem Inf Model 52:867–881PubMedCrossRefGoogle Scholar
  11. 11.
    Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455–461PubMedCentralPubMedGoogle Scholar
  12. 12.
    Rappe AK et al (1992) UFF, a full periodic table force field for molecular mechanics and molecular dynamics simulations. J Am Chem Soc 114:10024–10035CrossRefGoogle Scholar
  13. 13.
    O'Boyle NM et al (2011) Open Babel: an open chemical toolbox. J Cheminform 3:33PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Perryman AL et al (2010) A dynamic model of HIV integrase inhibition and drug resistance. J Mol Biol 397:600–615PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Hanwell MD et al (2012) Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform 4:17PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Muchmore SW et al (2010) Cheminformatic tools for medicinal chemists. J Med Chem 53:4830–4841PubMedCrossRefGoogle Scholar
  17. 17.
    Nicholls A (2008) What do we know and when do we know it? J Comput Aided Mol Des 22:239–255PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Integrative Structural and Computational BiologyThe Scripps Research InstituteLa JollaUSA
  2. 2.Chula VistaUSA

Personalised recommendations