Screening of potential phytocompounds against Atherosclerosis by directing Liver X Receptor alpha (LXRα): A computational manoeuvre

Abstract Liver X receptor alpha (LXRα) is a nuclear receptor family member that is expressed in the liver, and has gained pharmacological interest for its role in the reduction of atherosclerosis, a long-term inflammatory disorder that affects the artery wall and is characterized by alterations in lipid metabolism. LXRα activators appear to be promising targets for preventing and/or treating these pathological conditions. The current work intends to perform a computational analysis of the IMPPAT database with LXRα. This comprehensive study will serve as a foundation for the investigation of novel plant-derived LXRα agonists against atherosclerosis. LXRα (PDB ID: 3IPU) was used as a target molecule for docking analysis. The docking scores of top five phytocompounds from the IMPAAT database, namely Betaxanthin, Adlumidiceine, Miraxanthin III S, Lupinisoflavone E, and p -Coumaroyl triacetic acid, ranged from - 35.88 kcal/mol to - 32.46 kcal/mol. The docking analysis was validated further by a 100 ns molecular dynamics study, which revealed fewer fluctuations in RMSD along with stable intermolecular interactions of lead phytocompounds with the targeted LXRα protein. The enrichment calculation metrics also validated the efficiency of the docking procedure. As evidenced by the MM-GBSA study, the binding free energies (ΔG bind ) score up to -71.219 kcal/mol, with no violations in terms of drug likeliness and ADMET predictions, indicated the promising nature of these phytocompounds as drug candidates against atherosclerosis. These in silico studies, in particular, aid in analyzing phytocompounds roles as potential lead drugs, paving the way for in vitro and in vivo assessments for the development of novel anti-atherosclerosis drugs.