拮抗状态下α_(1A),α_(1B)和α_(1D)-肾上腺素能受体的分子模拟研究  

Receptor-based Molecular Modeling Study on Antagonist-Bound Human α_(1A),α_(1B)和α_(1D)-Adrenoceptors

作　　者：李敏勇[1] 卢景芬[2] 夏霖[1] 

机构地区：[1]中国药科大学药物化学教研室,南京210009 [2]北京大学天然药物与仿生药物重点实验室,北京100083

出　　处：《化学学报》2005年第20期1875-1883,共9页Acta Chimica Sinica

基　　金：863计划(No.2002AA2Z3118);北京大学天然药物与仿生药物重点实验室基金资助项目.

摘　　要：采用同源建模法对α1A-,α1B-和α1D-AR的三维结构进行了模拟,并采用分子力学、分子动力学方法对所得同源模型进行优化,然后分别采用训练集拮抗剂对接的方法得到拮抗状态下的α1A-,α1B-和α1D-AR三维结构模型.得到的模型再采用FRED对接软件对测试集中的18个化合物进行对接并打分,再将所得打分结果与其活性进行线性回归,其回归结果具有良好的拟合效果,由此回归方程预测的活性与化合物实验值较吻合,说明我们建立的拮抗状态下的α1A-,α1B-和α1D-AR的三维同源模型具有一定的合理性,可作为化合物虚拟筛选模型,对新化合物进行对接虚拟筛选.This investigation was performed to present the construction of rough homology models, the refinement using molecular methanics and molecular dynamics, and the optimization of these models into “antagonist-bound” models using training set docking for α1A1,α1B and α1D-AR models. A test set consisting of 18 molecules was then docked into to obtained “antagonist-bound” models using FRED program. The docking scores and experimental affinities were analyzed by linear regression to obtain a good correlation. Consequently, this work highlights the rational construction for “antagonist-bound” α1A1,α1B and α1D-AR models. The knowledge of these models can be used for virtual screening to discover more novel potential molecules.

关 键 词：肾上腺素能受体 拮抗剂 同源模型 分子模拟 分子对接 模拟研究 分子力学 状态 三维结构模型 分子动力学方法 

分 类 号：R91[医药卫生—药学]