Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ng R (2008) Drugs: from discovery to approval, 2nd edn. Wiley-Blackwell, Hoboken, NJ
Swinney DC, Anthony J (2011) How were new medicines discovered? Nat Rev Drug Discov 10:507–519
Jacob RB, Andersen T, McDougal OM (2012) Accessible high-throughput virtual screening molecular docking software for students and educators. PLoS Comput Biol 8:e1002499
Lindell SD, Pattenden LC, Shannon J (2009) Combinatorial chemistry in the agrosciences. Bioorg Med Chem 17:4035–4046
Varghese JN et al (1992) The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor. Proteins 14:327–332
McKimm-Breschkin JL (2013) Influenza neuraminidase inhibitors: antiviral action and mechanisms of resistance. Influenza Other Respir Viruses 7:25–36
Knox C et al (2011) DrugBank 3.0: a comprehensive resource for ‘omics’ research on drugs. Nucleic Acids Res 39:D1035–D1041
Li Q et al (2010) PubChem as a public resource for drug discovery. Drug Discov Today 15:1052–1057
Berman HM et al (2002) The protein data bank. Acta Crystallogr D Biol Crystallogr 58:899–907
Scior T et al (2012) Recognizing pitfalls in virtual screening: a critical review. J Chem Inf Model 52:867–881
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 31:455–461
Rappe AK et al (1992) UFF, a full periodic table force field for molecular mechanics and molecular dynamics simulations. J Am Chem Soc 114:10024–10035
O'Boyle NM et al (2011) Open Babel: an open chemical toolbox. J Cheminform 3:33
Perryman AL et al (2010) A dynamic model of HIV integrase inhibition and drug resistance. J Mol Biol 397:600–615
Hanwell MD et al (2012) Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform 4:17
Muchmore SW et al (2010) Cheminformatic tools for medicinal chemists. J Med Chem 53:4830–4841
Nicholls A (2008) What do we know and when do we know it? J Comput Aided Mol Des 22:239–255
Acknowledgements
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.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this protocol
Cite this protocol
Dallakyan, S., Olson, A.J. (2015). Small-Molecule Library Screening by Docking with PyRx. In: Hempel, J., Williams, C., Hong, C. (eds) Chemical Biology. Methods in Molecular Biology, vol 1263. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2269-7_19
Download citation
DOI: https://doi.org/10.1007/978-1-4939-2269-7_19
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-2268-0
Online ISBN: 978-1-4939-2269-7
eBook Packages: Springer Protocols