INVESTIGATION OF BIOACTIVE PHYTOCOMPUNDS FROM CARICAPAPAYA AND PEROXISOME PROLIFERATORS ACTIVATED RECEPTOR GAMMA (PPARƔ) USING 4R2U DURING OBESITY CONDITION

ABSTRACT Obesity is a global health challenge characterized by excessive fat accumulation and associated with numerous metabolic disorders, including type 2 diabetes, cardiovascular diseases, and certain cancers. The peroxisome proliferator-activated receptor gamma (PPARɣ) is a nuclear receptor that plays a critical role in adipogenesis, lipid metabolism, and glucose homeostasis, making it a promising target for anti-obesity therapeutics. Caricapapaya, a tropical fruit, is known for its rich phytochemical profile with potential health benefits. This study investigates the bioactive phytocompounds of Caricapapaya and their interaction with PPARɣ, specifically using the crystal structure 4R2U, to evaluate their efficacy in managing obesity.The primary objective of this study is to identify and evaluate bioactive phytocompounds from Caricapapaya for their potential as PPARɣ agonists using molecular docking simulations with the PPARɣ ligand-binding domain structure (PDB ID: 4R2U). The goal is to explore these compounds' therapeutic potential in ameliorating obesity and associated metabolic disorders.Phytocompounds were extracted from Caricapapaya leaves, seeds, and fruit using standard phytochemical extraction techniques. Molecular docking studies were conducted using Meastro to predict the binding affinity and interaction of these phytocompounds with the PPARɣ ligand-binding domain (PDB ID: 4R2U). The docking results were analyzed based on binding energy scores, hydrogen bonding interactions, and the stability of the ligand-receptor complexes. Additionally, molecular dynamics simulations were performed to assess the stability and conformational changes of the top-ranking ligand-PPARɣ complexes.Several phytocompounds from Caricapapaya demonstrated significant binding affinity to the PPARɣ receptor, with binding energy scores comparable to known PPARɣ agonists. Compounds such as Riboflavin, Rutin, and Ethyl_linolenate exhibited strong interactions with key amino acid residues within the PPARɣ ligand-binding domain. These interactions were predominantly hydrogen bonds and hydrophobic interactions, indicating stable and favorable binding. Molecular dynamics simulations further confirmed the stability of the ligand-PPARɣ complexes over a 50 ns simulation period, with minimal conformational fluctuations observed