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

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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.

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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).

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  1. Edithe Selwa, Eddy Elisée and Agustin Zavala have contributed equally to this work.

Authors and Affiliations

  1. Institut de Chimie des Substances Naturelles, CNRS UPR 2301, LabEx LERMIT, 91198, Gif-sur-Yvette, France

    Edithe Selwa, Eddy Elisée, Agustin Zavala & Bogdan I. Iorga

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  1. Edithe Selwa
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  2. Eddy Elisée
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Correspondence to Bogdan I. Iorga.

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Selwa, E., Elisée, E., Zavala, A. et al. Blinded evaluation of farnesoid X receptor (FXR) ligands binding using molecular docking and free energy calculations. J Comput Aided Mol Des 32, 273–286 (2018). https://doi.org/10.1007/s10822-017-0054-1

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