蛋白酪氨酸磷酸酶1B抑制剂的分子对接及三维定量构效关系研究

目的对文献报道的一系列芳环取代噻唑类蛋白酪氨酸磷酸酶1B(PTP1B)抑制剂进行分子对接及三维定量构效关系(3D-QSAR)研究。方法应用Surflex-Dock进行分子对接结合模式研究,并用比较分子力场分析(CoMFA)和比较分子相似性指数分析(CoMSIA)方法进行三维定量构效关系研究,建立具有良好预测能力的3D-QSAR模型。结果对接结果表明,该类结构可以很好地占据PTP1B的3个关键结合位点,大大提高了抑制剂与酶的亲和力。所建立的CoMFA模型交叉验证系数q~2为0.644,CoMSIA模型交叉验证系数q~2为0.719。结论获得的CoMFA和CoMSIA模型具有可靠的预测能力,可应用于指导该类化合物的设计。

Molecular docking and 3D-QSAR studies on protein tyrosine phosphatase 1B inhibitors

Objective 3D-QSAR and molecular docking studies were performed on a series of protein tyrosine phosphatase 1B inhibitors with the structure of the aromatic ring substituted 1,3-thiazole derivatives reported in the literatures.Methods Surflex-Dock was used to explore the binding modes.A 3D-QSAR study using CoMFA and CoMSIA techniques was carried out to explore the 3D-structure activity relationship of these molecules,from which the CoMFA and CoMSIA models were also established.Result Docking results showed that these structures occupied the 3 key binding sites of PTP1B,which could greatly enhance the affinity and selectivity of the enzyme with the substrates.The cross-validated values (q2) of the established CoMFA model and CoMSIA model are 0.644 and 0.719,respectively.Conclusion The established CoMFA and CoMSIA models have the convincing predictability,which could provide the direct guidance for the design of this kind of compounds as the postential PTP1B inhbitors.