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Volume 21, Issue 15
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background

Peroxisome proliferator-activated receptor-gamma (PPAR-γ) plays a crucial role in regulating lipid and glucose metabolism, cancer, and inflammation, making it an attractive target for drug development. Meanwhile, β-Carotene, known for its antioxidant, anticancer and anti-inflammatory properties, holds promise for modulating PPAR-γ activity. Understanding their interaction is crucial.

Objective

This study aims to explore the therapeutic potential of β-carotene in modulating PPAR-γ activity by investigating their binding interactions.

Methods

Screening of bioactive compounds from PubChem was conducted using GlideXP to identify potential PPAR-γ (PDB: 2PRG) ligands. During this screening, both protein and bioactive compounds were prepared following established protocols. Subsequently, the compounds were docked into the ligand binding domain (LBD) of the protein using XP docking. Rosiglitazone was used as an internal control. β-Carotene emerged as a lead based on Lipinski’s rule, docking score, free energy, and LBD interactions. Molinspiration analysis assessed its drug likeness. Molecular dynamics (MD) simulations utilizing Desmond with OPLS 2005 force field were employed to examine the dynamics and stability of the PPAR-γ/β-carotene complex.

Results

β-carotene had strong hydrophobic interactions with specific residues within the ligand-binding domain of PPAR-γ. The calculated binding affinity (-9.07 kcal/mol) indicated a strong interaction between β-carotene and PPAR-γ, suggesting that β-carotene may modulate the activity of PPAR-γ. On a time scale of 100 ns, the MD simulations provided insights into the conformational changes, flexibility, and intermolecular interactions within the complex.

Conclusion

docking and dynamics simulation analyses show that PPAR-γ and β-carotene can form a stable complex, suggesting potential implications for metabolic modulation.

© 2024 Bentham Science Publishers
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2023-10-31
2024-12-29

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In-silico Docking and Dynamics Simulation Analysis of Peroxisome Proliferator-Activated Receptor-Gamma and β-Carotene
Letters in Drug Design & Discovery 21, 3198 (2024); https://doi.org/10.2174/0115701808267878231026044212
/content/journals/lddd/10.2174/0115701808267878231026044212
/content/journals/lddd/10.2174/0115701808267878231026044212
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  • Article Type:     Research Article
Keyword(s): binding affinity; desmond; docking; glide; molecular dynamics; PPAR-γ; β-carotene

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