δ阿片受体与异硫氰基3-甲基芬太尼相互作用的分子模拟(英文)

Molecular modeling of interaction between δ opioid receptor and 3-methylfentanylisothiocyanate

目的:构建δ阿片受体(δOR)结构模型并研究它与异硫氰基3-甲基芬太尼(SuperFIT)的相互作用.方法:以细菌视紫红质为模板,模拟δOR的结构,并将SuperFIT对接于其内.结果:得到δOR-(3R,4S)-SuperFIT作用模型;其中,重要结合位点可能是Asp128,Ser106,Phe104,Tyr308及Pro315.Asp128与配基哌啶环上质子化氮原子形成强的静电和氢键相互作用;Ser106与配基异硫氰基N原子形成静电作用;Phe104,Tyr308及Pro315与异硫氰基S原子形成疏水作用.结论:Phe104,Tyr308,Pro315及Ser106对配基的δ选择性极重要,这将有利于设计新的δ选择性配基.

AIM: To construct a 3D structural model of 8 opioid receptor (δOR) and study its interaction with 3-methylfentanylisothiocyanate (SuperFIT). METHODS: Using the bacteriorhodopsin as a template, the 3D structure of δOR was modeled; SuperFIT was docked into its inside. RESULTS: The interaction model betweenδOR and (3R,4S)-SuperFIT was achieved, in which the important binding sites possibly were Asp128, Ser106, Phe104, Tyr308, and Pro315. Asp128 formed the electrostatic and hydrogen-binding interactions with the protonated nitrogen on piperidine of the ligand. Ser106 formed the electrostatic interaction with the N atom of isothiocyano group of the ligand; whereas Phe104, Tyr308, and Pro315 formed the hydrophobic interactions with the S atom of isothiocyano group. In addition, there were some other interactions between SOR and the ligand. CONCLUSION: The residues Phel04, Tyr308, Pro315, and Ser106 of SOR are crucial to the S selectivity of the ligand, which is beneficial for designing novel S-selective ligand.