α-芋螺毒素特异性结合受体-神经型烟碱乙酰胆碱受体的同源模建及功能预测

Neuronal nicontinic acetylcholine receptor-homology modeling and functional prediction of α-conotoxin-specific binding receptor

目的探讨神经型烟碱乙酰胆碱受体能被其竞争性拮抗剂α-芋螺毒素选择性阻断的机理。方法采用同源模建的方法构建神经型烟碱乙酰胆碱受体α-7亚型的三维空间结构,并利用分子对接的方法与已知空间构像的α-芋螺毒素对接。结果已构建的神经型烟碱乙酰胆碱受体α-7亚型结构合理,并与已知空间构像的α-芋螺毒素对接成功。结论传统的烟碱型乙酰胆碱受体拮抗剂缺乏专一性,而靶向神经元神经型烟碱乙酰胆碱受体的α-芋螺毒素种类多,特异性强,与不同亚单位组成的受体亲和力不同,应用潜力很大。

Purpose To explore the block mechanism of competitive antagonist whose neuronal nicotinic acetylcholine receptors（nAChRs） can be the competitive antagonist α-conotoxin PnIB further.Methods Homology modeling method is adopted to build nAChRs α-7 subtype of the three-dimensional structure and the molecular docking methods and the known spatial conformation of α-conotoxin docking are used.Results The results showed that building the structure of α-7 subtype of nAChRs is rational,and it has been docked with the known structure of α-conotoxin successfully.Conclusion Traditional nAChRs lack specificity,while there are many kinds of α-conotoxins targeting nAChRs which have different affinities and specificities,and they can be applied potentially.Thus,we hope that the method of molecular modeling is used where α-contoxin could be better for investigating the subtypes of nAChRs and developing new treatments for neurological diseases.