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Journal of Computer-Aided Molecular Design

, Volume 33, Issue 9, pp 817–829 | Cite as

Assessing and improving the performance of consensus docking strategies using the DockBox package

  • Jordane PretoEmail author
  • Francesco GentileEmail author
Article

Abstract

Molecular docking is a well-established computational technique that aims to predict how a ligand binds to a specific protein target, as well as to assess the strength of the binding. Although docking programs are used worldwide for drug discovery, it is not always simple to identify which program or combination of programs provides the best results for a target of interest. Here we present DockBox, a computational package designed to facilitate the use of multiple docking and scoring programs allowing to combine them using different consensus strategies. As part of the DockBox package, a new consensus docking method called score-based consensus docking (SBCD) is introduced. SBCD was found to significantly improve the pose prediction success rates of single docking programs. When applied to virtual screening, SBCD enhanced enrichment factors while producing higher hit rates than standard consensus docking (CD). SBCD can be run with almost no additional computational cost and time compared to CD, if the same docking programs are used for pose generation. Furthermore, SBCD allows the use of many scoring functions to assess consensus without significant overhead, making it a promising new approach for the screening of large chemical libraries. DockBox is an open-source package publicly available at https://pypi.org/project/dockbox.

Keywords

Docking software Scoring functions Consensus docking Computer-aided drug discovery Virtual screening Binding pose prediction 

Notes

Acknowledgements

We gratefully acknowledge support from the PSMN (Pôle Scientifique de Modélisation Numérique) of the ENS de Lyon for the computing resources. We also warmly thank Prof. Jack Tuszynski and Mr. Philip Winter for providing useful comments and proofreading the manuscript.

Author contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

Supplementary material

10822_2019_227_MOESM1_ESM.pdf (1.1 mb)
Supplementary material 1 (PDF 1079 kb)

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of OncologyUniversity of AlbertaEdmontonCanada
  2. 2.Department of PhysicsUniversity of AlbertaEdmontonCanada
  3. 3.INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de LyonUniversité Claude Bernard Lyon 1LyonFrance
  4. 4.Vancouver Prostate CentreUniversity of British ColumbiaVancouverCanada

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