小分子凝血酶抑制剂的分子设计与计算机模拟

Molecular design and computer simulation of small molecule thrombin inhibitor

目的设计5种小分子并研究其与凝血酶的对接,以研究新型凝血酶抑制剂。方法根据PPACK结构设计5种小分子凝血酶抑制剂,并通过autodock 4.2和MVD2010.4.0(molegro virtual docker)模拟这5种分子与凝血酶的对接。最后合成这5种分子,并测定凝血酶抑制剂的活性。结果 autodock对接数据显示分子1、2、5具有较高活性。MVD对接数据显示分子1、2、3具有较高活性。实验测定结果显示分子1、2、3、5均有一定活性。结论实验结果证明计算机模拟数据有一定的参考价值。

Objective To design 5 thrombin inhibitors and study the docking configuration between the inhibitors and thrombin,and to establish novel thrombin inhibitor.Methods Five thrombin inhibitors were designed based on the PPACK structure,and the docking configuration between the inhibitors and thrombin was studied by autodock 4.2 and MVD 2010.4.0.The thrombin inhibitors were synthesized and the actual inhibitory ratio determined.Results Autodock docking data showed molecule 1,2 and 5 were active,while the MVD data showed molecule 1,2 and 3 were active.The actual inhibitory ratio showed that molecule1,2,3 and 5 were all active.Conclusion The computer simulation data are valuable.