Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, 100193, China.
J Mol Model. 2019 Jun 1;25(6):175. doi: 10.1007/s00894-019-4067-7.
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 = 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.
在这项研究中，进行了分子对接研究，以探索钠-葡萄糖协同转运蛋白 2（SGLT2）与其抑制剂的结合相互作用。观察到对接评分与实验生物活性之间存在相关性（R=0.8368，N=24）。使用三维定量构效关系（3D-QSAR）方法设计了新的抑制剂，并通过对接方法预测了它们的活性。为了了解化合物 1m（对接评分最高）和化合物 1t（对接评分最低）的构效关系，我们进行了组合分子动力学模拟和 MM-GBSA 方法。结果发现，在 SGLT2-1m 系统中，Gln271 和 Val272 之间的相互作用表现出显著的影响，而在 SGLT2-1t 系统中则不存在。这项研究有望揭示化合物 1m 的作用机制，为开发针对 SGLT2 的活性药物候选物提供指导。
