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Molecular Modeling Approach to Study the PPARγ–Ligand Interactions

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Nuclear Receptors

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1966))

Abstract

The chapter is focused on methods relevant for predictive toxicology and computer-aided drug design (adverse outcome pathway development, pharmacophore modeling, docking, and 3D QSAR analysis) and applied to study interactions between peroxisome proliferator-activated receptor γ (PPARγ) and its ligands. The methods have been combined to develop an integrated in silico approach allowing both to predict potential PPARγ-mediated hepatotoxicity of receptor’s full agonists, thus supporting hazard characterization, and to identify naturally derived antidiabetic triterpenoids potentially acting through PPARγ partial agonism.

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Notes

  1. 1.

    Only in the in vitro systems achieving of a real equilibrium is suggested, since all other experimental settings involve time-dependent changes, due to cross-relation with other biochemical events (e.g., membrane permeation) and dependence of diffusion gradients and transport phenomena.

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Acknowledgments

The authors would like to acknowledge the support of the European Community’s seventh Framework Program (FP7/2007–2013) COSMOS Project under grant agreement no. 266835, the Cosmetics Europe, and the National Science Fund of Bulgaria grant agreement no. DM 01/1/2016.

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Author notes

  1. Merilin Al Sharif and Ivanka Tsakovska contributed equally to this work.

Authors and Affiliations

  1. Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria

    Merilin Al Sharif, Ivanka Tsakovska, Petko Alov, Antonia Diukendjieva & Ilza Pajeva

  2. Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria

    Vessela Vitcheva

Authors
  1. Merilin Al Sharif
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  2. Ivanka Tsakovska
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  3. Petko Alov
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  4. Vessela Vitcheva
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  5. Antonia Diukendjieva
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  6. Ilza Pajeva
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Corresponding author

Correspondence to Ilza Pajeva .

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Editors and Affiliations

  1. School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA

    Mostafa Z. Badr

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Al Sharif, M., Tsakovska, I., Alov, P., Vitcheva, V., Diukendjieva, A., Pajeva, I. (2019). Molecular Modeling Approach to Study the PPARγ–Ligand Interactions. In: Badr, M. (eds) Nuclear Receptors. Methods in Molecular Biology, vol 1966. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9195-2_22

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  • DOI: https://doi.org/10.1007/978-1-4939-9195-2_22

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