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Docking simulations suggest that all-trans retinoic acid could bind to retinoid X receptors

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Abstract

Retinoid X receptors (RXRs) are ligand-controlled transcription factors which heterodimerize with other nuclear receptors to regulate gene transcriptions associated with crucial biological events. 9-cis retinoic acid (9cRA), which transactivates RXRs, is believed to be an endogenous RXR ligand. All-trans retinoic acid (ATRA) is a natural ligand for retinoic acid receptors (RARs), which heterodimerize with RXRs. Although the concentration of 9cRA in tissues is very low, ATRA is relatively abundant and some reports show that ATRA activates RXRs. We computationally studied the possibility of ATRA binding to RXRs using two different docking methods with our developed programs to assess the binding affinities of naturally occurring retinoids. The simulations showed good correlations to the reported binding affinities of these molecules for RXRs and RARs.

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Abbreviations

ATRA:

All-trans retinoic acid

9cRA:

9-cis retinoic acid

13cRA:

13-cis retinoic acid

RAR:

Retinoic acid receptor

RXR:

Retinoid X receptor

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Author contributions

KS., M.T., and H.K. designed the experiments. M.T. performed the experiments and analyzed data. M.T. wrote the paper. All authors approved the manuscript.

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Authors and Affiliations

  1. Institute of Molecular Function, 2-105-14 Takasu, Misato-shi, Saitama, 341-0037, Japan

    Motonori Tsuji

  2. Japan Pharmaceutical Information Center, 2-12-15 Shibuya, Shibuya-ku, Tokyo, 150-0002, Japan

    Koichi Shudo

  3. Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-0062, Japan

    Hiroyuki Kagechika

Authors
  1. Motonori Tsuji
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  2. Koichi Shudo
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  3. Hiroyuki Kagechika
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Corresponding author

Correspondence to Motonori Tsuji.

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10822_2015_9869_MOESM1_ESM.pdf

Receptor-rigid and ligand-flexible docking simulations using Autodock Vina and Sievgene programs and ROC curves for the biomacromolecule-rigid and ligand-flexible docking simulations using Docking Study with HyperChem program (PDF 443 kb)

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Tsuji, M., Shudo, K. & Kagechika, H. Docking simulations suggest that all-trans retinoic acid could bind to retinoid X receptors. J Comput Aided Mol Des 29, 975–988 (2015). https://doi.org/10.1007/s10822-015-9869-9

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  • DOI: https://doi.org/10.1007/s10822-015-9869-9

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