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Journal of Computer-Aided Molecular Design

, Volume 32, Issue 1, pp 151–162 | Cite as

Docking of small molecules to farnesoid X receptors using AutoDock Vina with the Convex-PL potential: lessons learned from D3R Grand Challenge 2

  • Maria Kadukova
  • Sergei GrudininEmail author
Article

Abstract

The 2016 D3R Grand Challenge 2 provided an opportunity to test multiple protein–ligand docking protocols on a set of ligands bound to farnesoid X receptor that has many available experimental structures. We participated in the Stage 1 of the Challenge devoted to the docking pose predictions, with the mean RMSD value of our submission poses of 2.9 Å. Here we present a thorough analysis of our docking predictions made with AutoDock Vina and the Convex-PL rescoring potential by reproducing our submission protocol and running a series of additional molecular docking experiments. We conclude that a correct receptor structure, or more precisely, the structure of the binding pocket, plays the crucial role in the success of our docking studies. We have also noticed the important role of a local ligand geometry, which seems to be not well discussed in literature. We succeed to improve our results up to the mean RMSD value of 2.15–2.33 Å  dependent on the models of the ligands, if docking these to all available homologous receptors. Overall, for docking of ligands of diverse chemical series we suggest to perform docking of each of the ligands to a set of multiple receptors that are homologous to the target.

Keywords

Protein–ligand docking Ensemble docking Flexible docking D3R Scoring function 

Notes

Acknowledgements

The authors thank Vladimir Chupin from MIPT Moscow for helpful discussions during the development of the Convex-PL potential. The authors also thank Andreas Eisenbarth from the University of Kaiserslautern for the development of docking protocols. This work was partially supported by the Ministry of Education and Science of the Russian Federation (No. 6.3157.2017/PP).

Supplementary material

10822_2017_62_MOESM1_ESM.pdf (113 kb)
Supplementary material 1 (pdf 112 KB)

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Univ. Grenoble Alpes, LJKGrenobleFrance
  2. 2.CNRS, LJKGrenobleFrance
  3. 3.InriaGrenobleFrance
  4. 4.Moscow Institute of Physics and TechnologyDolgoprudnyRussia

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