In-silico studies on structural function of ampk through docking approach toward design drug for atherosclerosis

Abstract

Atherosclerosis poses significant health risks, driving cardiovascular issues like heart attacks and strokes. Shortage of appropriate pathophysiological models and a suitable algorithm for the discovery of drugs and para-pharmaceuticals with direct anti-atherosclerotic action are major barriers to the effective pathogenetic medication for atherosclerosis. This study focused on using bioinformatics tools and molecular docking techniques to identify novel molecular agonists for the Activated Monophosphate Kinase (AMPK) enzyme via the AMPK/PP2A/NF-κB/LOX-1 pathway. Virtual screening and molecular docking were performed for activation and phosphorylation of AMPK and stimulation of Protein Phosphostase-2A (PP2A) which results in down-regulation of lectin-like oxLDL (LOX-1) receptor to reduce the internalization of oxidized low-density lipoprotein (oxLDL). Enkephalin (ZINC000014952116) emerged as a potent AMPK agonist, triggering a cascade of interactions leading to reduced LOX-1 expression and which inhibits the Nuclear Factor kappa betta (NF-κβ) transcriptional activity for inflammatory atherosclerosis.