Abstract: The molecular docking study of 20 small-molecule monosaccharides and their analogues with α-glucosidase was carried out with AutoDock 4.2 software. The relationship between the binding free energy and the half-maximum inhibitory concentration (IC50) was analyzed, and the molecular structure of the inhibitor was further optimized according to the interaction between the receptor and the ligand. The results showed that the amino acid residues Asp542, Asp443, His600, Asp327 and Arg526 in α-glucosidase were important sites for hydrogen bonding between each of the compounds and the enzyme. After replacing the O atom on the sugar ring with N or C atoms, the binding free energy of the former became smaller, and the binding of ligand to the receptor was stronger. The docking results after the molecular structure modification of validamine showed that the N atom on the six-membered ring and the presence of the –NH2 substituent on the ring played a very important role in the docking of the molecules with α-glucosidase. This study provides a new idea for the screening and optimized design of high-efficiency α-glucosidase inhibitors in the future.

Key words: α-glucosidase, inhibitor, molecular docking, small molecule construction