μ阿片受体及其与羟甲芬太尼相互作用的分子模拟(英文)

Molecular modeling of μ opioid receptor and its interaction with ohmefentanyl

目的:建立μ阿片受体的结构模型,并结合模型研究羟甲芬太尼对该受体的作用机制。方法:以细菌视紫红质的三维结构为模板,在计算机上建立μ阿片受体模型,然后将羟甲芬太尼对接到假想的受体结合部位。结果:得到了良好的配体-受体相互作用模型,发现残基Asp147与His319为可能的结合位点。配体质子化N原子与Asp147形成强的静电和氢键相互作用,羰基O原子与His319形成弱的静电和氢键相互作用,两个苯环分别与周围的芳香残基形成π-π相互作用。结论:该配体-受体相互作用模型有助于合理设计新型镇痛药。

AIM:To build up the structure model of μ opioid receptor, then combined with the receptor model, to investigate the action mechanism of ohmefentanyl on the receptor. METHODS: Using the three-dimensional structure of bacteriorhodopsin as a template, we constructed μ opioid receptor model on computer. Ohmefentanyl was then docked into the supposed receptor binding sites. RESULTS: A good ligand-receptor interaction model was achieved. The possible binding sites were found to be Aspl47 and His319. The protonated N atom of ohmefentanyl form potent electrostatic and hydrogen-bonding interactions with residue Aspl47 of the receptor, the O atom of the carbonyl group form weak electrostatic and hydrogen-bonding interactions with residue His319, and the two phenyl groups form π-π interactions with some aryl residues of the receptor around ligand. CONCLUSION: The ligand-receptor interaction model should be helpful for rational design of novel analgesic.