Tang Y, Chen K X, Jiang H L, Jin G Z, Ji R Y
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
Zhongguo Yao Li Xue Bao. 1996 Jan;17(1):8-12.
To build up the structure models of dopamine receptors, then combined with the receptor models, to investigate the action mechanism of tetrahydroprotoberberines (THPB) on dopamine receptors at the molecular level.
Using the three-dimensional structure of bacteriorhodopsin as a template, we have constructed dopamine D1 and D2 receptor models on computer. l-Stepholidine was selected as the leading compound of THPB and docked into D1 and D2 receptor active sites.
After manual adjustment and energy minimization, the ligand-receptor interaction models were achieved. Based on these models, the possible action mechanism of THPB on dopamine receptors was suggested that the protonated N atom of THPB form electrostatic interaction and hydrogen-bonding interaction with residue Asp in TM3 of the receptor, the two substituents in D ring of THPB form hydrogen-bonding interactions with two Ser residues in TM5 of the receptor, and the aryl groups form pi-pi interactions with some aryl residues of the receptor around ligand.
Our ligand-receptor interaction models should be helpful for rational design of more potent drugs.
构建多巴胺受体的结构模型，然后结合受体模型，在分子水平上研究四氢原小檗碱（THPB）对多巴胺受体的作用机制。
以细菌视紫红质的三维结构为模板，在计算机上构建多巴胺D1和D2受体模型。选择l-千金藤啶碱作为THPB的先导化合物，并将其对接至D1和D2受体活性位点。
经过人工调整和能量最小化，得到配体-受体相互作用模型。基于这些模型，推测THPB对多巴胺受体的可能作用机制为：THPB的质子化N原子与受体TM3中的天冬氨酸残基形成静电相互作用和氢键相互作用；THPB的D环中的两个取代基与受体TM5中的两个丝氨酸残基形成氢键相互作用；芳基与配体周围受体的一些芳基残基形成π-π相互作用。
我们的配体-受体相互作用模型应有助于更有效药物的合理设计。
