design and evaluation of novel small molecule activators for ampk: an in-silico approach

Amp-activated protein kinase (ampk) plays an important role in regulating energy homeostasisin eukaryotic cells. ampk is an attractive therapeutic target for managing metabolic diseases suchas type 2 diabetes and cancers[1-3]. nowadays, in silico study and evaluations are applied throughvirtual screening tools, such as molecular docking simulations and predictions of admet-relatedproperties to investigate new potent activators for target proteins. the molecular dockingsimulation is performed to achieve the best binding affinity and docking scores. this is done bycomparison between the standard recently reported activator and high-scoring selected ligands.using data servers’ libraries as pubchem, some similar compounds selected and simulationmolecular docking has occurred. active site was studied and newly selected ligands were appliedto molecular docking simulation in active site and other active cavities in target protein. the resultswere evaluated and high quantities in binding affinities were selected as candidate ligands. thenprediction of admet related properties occurred using admetlab 2.0 and prediction resultswere compared with molecular docking results. finally, 5-[[6-chloro-5-(3-methyl-1h-indol-5-yl)-1h-benzimidazol-2-yl]oxy]-2-methylbenzoic acid and 6-[2-(3-carboxy-4-methylphenoxy)-6-chloro-1h-benzimidazol-5-yl]-3-methylindole-1-carboxylic acid have best results and must beconsiderate as potent activator for amp-activated protein kinase