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目的:研究芬太尼类配体(FA)的溶剂化效应以及和μ阿片受体的相互作用机制。方法:将芬太尼类配体进行溶剂化,柔性对接到μOR的七个α螺旋束之内,计算结合能并进行CoMFA和QSAR研究。结果:(1)得到FA的溶剂化模型。(2)得到FA与μOR相互作用的模型,FA通过静电作用、氢键和疏水作用与μOR结合。(3)描述了μOR中适合于FA的结合口袋,主要位于μOR的第3,4,5,6,7跨膜螺旋中,形成口袋的主要残基为Ile144,Asp147,Tyr148,Met151,Trp192,Leu200,Ile238,Ile242,His297,Val300,Tyr326,Ser329。(4)FA-μOR的结合能与FA的镇痛活性之间有很好的相关性。结论:该研究有助于全面了解FA与μOR的相互作用机理和设计新的镇痛化合物。
Objective: To study the solvation effect of fentanyl ligand (FA) and its interaction with mu opioid receptor. METHODS: Fentanyl ligands were solvated and flexibly docked into seven α-helix bundles of μOR. The binding energies were calculated and CoMFA and QSAR studies were performed. Results: (1) The solvation model of FA was obtained. (2) A model of the interaction between FA and μOR is obtained. FA combines with μOR through electrostatic interaction, hydrogen bonding and hydrophobic interaction. (3) The binding pocket of μOR suitable for FA is described, mainly in the 3, 4, 5, 6, 7 transmembrane helices of μOR. The major residues forming the pocket are Ile144, Asp147, Tyr148, Met151, Trp192, Leu200, Ile238, Ile242, His297, Val300, Tyr326, Ser329. (4) There is a good correlation between FA-μOR binding energy and FA analgesic activity. Conclusion: This study helps to fully understand the interaction mechanism between FA and μOR and to design new analgesic compounds.