In-silico Docking and Dynamics Simulation Analysis of Peroxisome Proliferator-Activated Receptor-Gamma and -Carotene

Background Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) plays a crucial role in regulating lipid and glucose metabolism, cancer, and inflammation, making it an attractive target for drug development. Meanwhile, beta-Carotene, known for its antioxidant, anticancer and anti-inflammatory properties, holds promise for modulating PPAR-gamma activity. Understanding their interaction is crucial.Objective This study aims to explore the therapeutic potential of beta-carotene in modulating PPAR-gamma activity by investigating their binding interactions.Methods Screening of bioactive compounds from PubChem was conducted using GlideXP to identify potential PPAR-gamma (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. beta-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-gamma/beta-carotene complex.Results beta-carotene had strong hydrophobic interactions with specific residues within the ligand-binding domain of PPAR-gamma. The calculated binding affinity (-9.07 kcal/mol) indicated a strong interaction between beta-carotene and PPAR-gamma, suggesting that beta-carotene may modulate the activity of PPAR-gamma. On a time scale of 100 ns, the MD simulations provided insights into the conformational changes, flexibility, and intermolecular interactions within the complex.Conclusion In silico docking and dynamics simulation analyses show that PPAR-gamma and beta-carotene can form a stable complex, suggesting potential implications for metabolic modulation.