A molecular dynamic study of furofuran lignans as an inhibitor of antidiabetic drug target

Abstract

An earlier research study has found that furofuran type lignans have exhibited an alpha-glucosidase inhibition. In this study, molecular docking and molecular dynamics simulation were carried out to investigate the interaction between furofuran lignan derivatives and human maltase. In the system simulation, four compounds were chosen, namely α-8 b, α-14, β-14 and compound 4. The simulation of the maltase-acarbose model system was used as a control study and comparison. The results showed that the binding characteristics of all 4 compounds were similar to that of acarbose by orienting the 3 , 4 - dihydroxyphenyl group towards the binding pocket and forming the hydrogen bonds with the amino acid residues within the binding site. However, the water molecules in the crystal structure were found to enhance the stability of the inhibitors in the binding site. From the calculated results, the free energies of the binding between the inhibitors and the maltase were in the following order: maltase-β-14 > maltase-α-14 > maltase-α-8b, which is consistent with the experimentallydetermined IC₅₀ values.