VIRTUAL SCREENING STUDIES OF SEAWEED METABOLITES FOR PREDICTING POTENTIAL PPARÎ³ AGONISTS
Objective: Peroxisome Proliferator-Activated Receptor-gamma (PPARÎ³) is a crucial nuclear hormone receptor, which modulates the transcriptional regulation of lipid and glucose homeostasis. It plays a crucial role in many of the metabolic and inflammatory systems. It is a key target for many of the anti-diabetic medications. Perturbation of PPARÎ³ activity is also observed in many of the cancers involving colon, breast, gastric and lung. Thus, it is considered to be the hub molecule for targeting many of these cellular disorders. Seaweed metabolites have been well documented to be novel structural entities with a broad spectrum of pharmacological values. However, it is yet to be utilized for screening PPARÎ³ agonists.
Methods: In this study, virtual screening of PPARÎ³ Ligand Binding Domain (LBD) was performed against the datasets from SeaWeed Metabolite Database (SWMD) using Schrodinger Glide High Throughput Virtual Screening module to identify potential PPARÎ³ agonists. Further, the most potential lead was also subjected to molecular dynamics simulation to infer the stability of complex formation.
Results: The results have revealed that bromophenolic compounds from the genus Avrainvillea to interact with documented key residues of LBD involved in agonist interactions. Many other metabolites from the genus Rhodomela, Leathesia, Bifurcaria, Osmundaria, Cymopolia also showed significant interactions with LBD of PPARÎ³.
Conclusion: The insights from this study will pave the way for further exploration of lead compounds from seaweed metabolites targeting PPARÎ³.
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