Three-dimensional models for β-adrenergic receptor complexes with agonists and antagonists
Three-dimensional models for β-adrenergic receptor complexes with agonists and antagonists
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DOI：
10.1021/jm0301437
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发表时间：
2003-10-09
影响因子：
7.3
通讯作者：
Lybrand, TP
中科院分区：
文献类型：
--
作者：
Furse, KE;Lybrand, TP
分子模拟方法已被用于构建β-肾上腺素能受体激动剂和拮抗剂复合物的三维模型。最近的视紫红质晶体结构被用作标准同源建模方法的模板。基于视紫红质的同源性模型进行了评估，与P-肾上腺素能受体的实验结果一致，并与使用从头建模技术开发的受体模型进行了比较。虽然从头和同源衍生的受体模型通常非常相似，但存在一些局部结构差异，这些差异显著影响推定的配体结合位点。从头受体模型似乎提供了更好的协议与实验数据，特别是受体复合物与激动剂配体。从头受体模型也产生了一些有趣的和可检验的β-肾上腺素能受体亚型配体选择性的结构基础的假设。
Molecular modeling methods have been used to construct three-dimensional models for agonist and antagonist complexes with beta-adrenergic receptors. The recent rhodopsin crystal structure was used as a template in standard homology modeling methods. The rhodopsin-based homology models were assessed for agreement with experimental results for P-adrenergic receptors, and compared with receptor models developed using de novo modeling techniques. While the de novo and homology-derived receptor models are generally quite similar, there are some localized structural differences that impact the putative ligand-binding site significantly. The de novo receptor models appear to provide much better agreement with experimental data, particularly for receptor complexes with agonist ligands. The de novo receptor models also yield some interesting and testable hypotheses for the structural basis of beta-adrenergic receptor subtype ligand selectivity.