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目的:研究孤啡肽和阿片类配体与阿片孤儿受体相 互作用的分子机制。方法:用分子动力学方法计算孤啡肽的最低能构象;通过分子对接程序将孤啡肽、阿片类配体对接到阿片孤儿受体的结合口袋中;通过结合能的计算研究配体对受体的亲和力与它们的结合能之间的关系。结果:孤啡肽(1-4)残基位于结合口袋的底部,孤啡肽(5-7)残基位于结合口袋的顶部,孤啡肽(8-17)残基与孤儿受体的第二膜外环区结合;阿片类配体和孤儿受体的结合方式与孤啡肽的情况类似,区别在于孤儿受体参与配体结合的残基种类和数量不同,因而亲和力不同;配体-受体的结合能与配体的亲和力之间有很好的相关性;预测了洛芬太尼四个异构体与阿片孤儿受体的亲和力。结论:该研究能够解释许多实验事实,有助于进一步理解阿片受体与配体相互作用的分子机制并设计新的分子生物学实验。
AIM: To investigate the molecular mechanism of orphanin and opioid ligand interaction with opioid orphan receptors. METHODS: The lowest conformation of orphanin was calculated by molecular dynamics method. Orphanin peptide and opioid ligand were docked into the binding pocket of opioid orphan receptor by molecular docking procedure. The binding energy The relationship between body’s affinities and their binding energy. RESULTS: The orphan peptide (1-4) residue was located at the bottom of the binding pocket and the orphanin peptide (5-7) residue was located at the top of the binding pocket. The orphan peptide (8-17) Two membrane outer ring zone; opioid ligand and orphan receptor binding mode and the case of orphanin peptide is similar, the difference is that orphan receptors involved in ligand binding residues of different types and amounts, and thus different affinity; ligand - There is a good correlation between the binding energy of the receptor and the affinity of the ligand; the affinity of the four isomers of lofapentane for orphan receptors is predicted. Conclusion: This study can explain many experimental facts and help to further understand the molecular mechanism of opioid receptor-ligand interaction and design new molecular biology experiments.