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Journal of Computer-Aided Molecular Design

, Volume 32, Issue 1, pp 273–286 | Cite as

Blinded evaluation of farnesoid X receptor (FXR) ligands binding using molecular docking and free energy calculations

  • Edithe Selwa
  • Eddy Elisée
  • Agustin Zavala
  • Bogdan I. IorgaEmail author
Article

Abstract

Our participation to the D3R Grand Challenge 2 involved a protocol in two steps, with an initial analysis of the available structural data from the PDB allowing the selection of the most appropriate combination of docking software and scoring function. Subsequent docking calculations showed that the pose prediction can be carried out with a certain precision, but this is dependent on the specific nature of the ligands. The correct ranking of docking poses is still a problem and cannot be successful in the absence of good pose predictions. Our free energy calculations on two different subsets provided contrasted results, which might have the origin in non-optimal force field parameters associated with the sulfonamide chemical moiety.

Keywords

Docking Scoring function Gold Vina Autodock Farnesoid X receptor FXR D3R Drug design data resource Grand Challenge 2 

Notes

Acknowledgements

We thank Prof. Bert de Groot for helpful discussions. The comments and suggestions of the reviewers are also acknowledged, as they greatly contributed to improve the manuscript. This work was supported by the Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT) [Grant No. ANR-10-LABX-33], by the JPIAMR transnational project DesInMBL [Grant No. ANR-14-JAMR-0002] and by the Région Ile-de-France (DIM Malinf).

Supplementary material

10822_2017_54_MOESM1_ESM.pdf (6.2 mb)
Supplementary material 1 (PDF 6324 KB)

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Institut de Chimie des Substances Naturelles, CNRS UPR 2301, LabEx LERMITGif-sur-YvetteFrance

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