Huang X Q, Jiang H L, Luo X M, Rong S B, Gu J D, Tan X J, Zhu Y C, Chen K X, Ji R Y, Cao Y
Shanghai Institute of Materia Medica, Shanghai 200031, China.
Acta Pharmacol Sin. 2000 Jan;21(1):46-54.
To do theoretical study about solvation effect and interaction mechanism of fentanyl analogs (FA) to mu opioid receptor (microOR).
Flexible docking (FlexiDock) was performed by using the possible active conformations of FA and optimized 3D structure of mu opioid receptor. Binding energies were calculated. Comparative molecular force field analysis (CoMFA) and quantitative structure activity relationship (QSAR) studies were carried out based on results of flexible docking. Solvation effects were considered by studying interaction of FA with water molecules. Partial least square (PLS) analysis was used to calculate regression equation for analgesic activities using binding energies as descriptive factor.
The nature of the correlation between the binding affinities and analgesic activities of FA was explained by our modeling result.
对芬太尼类似物（FA）与μ阿片受体（μOR）的溶剂化效应及相互作用机制进行理论研究。
利用FA可能的活性构象和优化后的μ阿片受体三维结构进行柔性对接（FlexiDock），计算结合能。基于柔性对接结果开展比较分子力场分析（CoMFA）和定量构效关系（QSAR）研究。通过研究FA与水分子的相互作用来考虑溶剂化效应。采用偏最小二乘法（PLS）分析，以结合能作为描述因子计算镇痛活性的回归方程。
1）通过柔性对接得到的这些类似物的结合构象合理。2）FA最有可能以结合构象的形式存在于水溶液中。3）能量计算和QSAR分析表明，FA计算得到的结合能与其镇痛活性之间具有良好的相关性。4）基于三维模型，可以合理阐释FA与μ阿片受体可能的相互作用机制。
我们的建模结果解释了FA结合亲和力与镇痛活性之间相关性的本质。
