Interaction of carbohydrate derivatives and sodium-glucose cotransporters 2 by molecular dynamic simulation / 中草药

ABSTRACT

Objective: To investigate the interactions between carbohydrate derivatives and sodium-glucose cotransporters 2 (SGLT2) using molecular dynamic (MD) method and to explore the mechanisms and structure-activity relationship of SGLT2 inhibitors. Methods: The homologous structure of SGLT2 was modeled, the GROMACS program was used to model eight structures, such as SGLT2, SGLT2-glucose compound, and SGLT2-carbohydrate compound. And the root mean square fluctuation (RMSF) of the key residues and ligands and the interaction energy between the ligands and SGLT2 was investigated by trajectory analysis. Results: The interaction energy calculated by MD method had the higher correlation with experimental results than that by molecular docking method. H80, K154, D158, and Y290 were the key residues involved in the interaction, N75 and F453 were the important residues, and W291, Q295, and S393 might be the auxiliary residues. The ligands had a relatively consistent conformation, and fragments A and C played the more important roles in receptor binding. And the size, rigidity, and polarity increasing could elevate the bonding strength. Conclusion: MD simulation results could display the good performance of the interaction between the ligands and SGLT2, and could give clear guidance for the design of new SGLT2 inhibitors.