A Novel Method for Drug Screen to Regulate G Protein-Coupled Receptors in the Metabolic Network of Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder and the pathogenesis of AD is poorly understood. G protein-coupled receptors (GPCRs) are involved in numerous key AD pathways and play a key role in the pathology of AD. To fully understand the pathogenesis of AD and design novel drug therapeutics, analyzing the connection between AD and GPCRs is of great importance. In this paper, we firstly build and analyze the AD-related pathway by consulting the KEGG pathway of AD and a mass of literature and collect 25 AD-related GPCRs for drug discovery. Then the ILbind and AutoDock Vina tools are integrated to find out potential drugs related to AD. According to the analysis of DUD-E dataset, we select five drugs, that is, Acarbose (ACR), Carvedilol (CVD), Digoxin (DGX), NADH (NAI), and Telmisartan (TLS), by sorting the ILbind scores (≥0.73). Then depending on their AutoDock Vina scores and pocket position information, the binding patterns of these five drugs are obtained. We analyze the regulation function of GPCRs in the metabolic network of AD based on the drug screen results, which may be helpful for the study of the off-target effect and the side effect of drugs.