目的:研究抗感染药物作用新靶点CrtN的结构及其与抑制剂萘替芬的作用机制,为新型CrtN抑制剂的发现奠定基础.方法:采用同源模建获得CrtN的三维结构,然后用分子动力学方法优化初始结构,并用Ramachandran图评估结果,最后通过活性位点搜索、分子对接和动力学模拟研究抑制剂萘替芬与CrtN的作用模式.结果:通过同源模建和动力学优化获得合理的CrtN结构用于药物与靶点的相互作用研究.对CrtN进行活性位点搜索,确定Site4口袋作为萘替芬的结合位点.通过分子对接及动力学模拟发现萘替芬与M51、P53、I55、I85、P146、Y150、Y190、L311、L376等形成疏水作用,与Y354形成阳离子-π键作用.结论:首次对CrtN的三维结构进行研究,阐明了疏水和阳离子-π键作用是萘替芬对CrtN产生抑制活性的重要分子基础.%Objective:To study the structure of anti-infective new target CrtN and its interactions with the inhibitor naftifine,thus providing insights into the design of new CrtN inhibitors.Methods:The structure of CrtN was built using homology modeling and optimized by molecular dynamics,and its quality was estimated by Ramachandran plot.Through binding site prediction and docking and molecular dynamics,the interaction mode of CrtN with its inhibitor naftifine was investigated.Results:After homology modeling and molecular dynamics,the reasonable structure of CrtN was obtained.Binding site prediction showed Site 4 of CrtN was the binding site of naftifine.Docking and molecular dynamics suggested that naftifine formed hydrophobic interactions with MS1,P53,I55,I85,P146,Y150,Y190,L311 and L376,and cation-π interaction with Y354.Conclusion:This study shows the hydrophobic interactions and cation-π may be the main interactions resulting in inhibitory activity of naftifine against CrtN.
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