公共化学
虚拟筛选
化学
药物发现
对接(动物)
化学
蛋白质酪氨酸磷酸酶
活动站点
计算生物学
药效团
组合化学
生物化学
酪氨酸
酶
生物
医学
护理部
作者
Dan Zhao,Lu Sun,Shijun Zhong
标识
DOI:10.1007/s11030-021-10323-2
摘要
Protein tyrosine phosphatase 1B (PTP1B) acts as a therapeutic target for type 2 diabetes. However, the major challenges of PTP1B drug discovery are the poor selectivity and the weak oral bioavailability. In this study, we performed a combined virtual screening approach including multicomplex pharmacophore, molecular docking-based screening, van der Waals energy normalization, pose scaling factor, ADMET evaluation, and molecular dynamics simulation to select PTP1B inhibitors from three databases (PubChem, ChEMBL, and ZINC). We identified three potential PTP1B inhibitors, compounds 1, 4, and 5, with favorable binding energy and good oral bioavailability. The energetic and geometrical analyses show that the three compounds are stably bound to PTP1B, via occupying both the catalytic site (site A) and the proximal noncatalytic site (site B or C). Such occupancy may improve the selectivity. This work not only provided a feasible virtual screening protocol, but also suggested three potential PTP1B inhibitors for the treatment of type 2 diabetes.
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