Development of sodium glucose co-transporter 2 (SGLT2) inhibitors with novel structure by molecular docking and dynamics simulation
Journal of Molecular Modeling(2019)
摘要
In this study, molecular docking studies were carried out to explore the binding interactions of sodium glucose co-transporter 2 (SGLT2) with its inhibitors. A correlation between the docking scores and the experimental bioactivity was observed (R 2 = 0.8368, N = 24). The new inhibitors were designed using the 3D quantitative structure activity relationship (3D-QSAR) method, and the activities were predicted by the docking method. In order to understand the structure–activity correlation of compound 1 m (the highest score of docking) and compound 1 t (the lowest score), we carried out a combined molecular dynamics simulation and MM-GBSA method. It was found that, in the system of SGLT2-1 m, the interaction between Gln271 and Val272 exhibited significant effects, which were absent in the SGLT2-1 t system. This study is expected to shed light on the mechanism of action of compound 1 m, leading to development of active drug candidates targeting SGLT2.
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关键词
SGLT2, Molecular docking, 3D-QSAR, Molecular dynamics simulation, Free energy calculation, Decomposition free energy calculation
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