Wurtz J M, Egner U, Heinrich N, Moras D, Mueller-Fahrnow A
Laboratoire de Biologie Structurale, IGBMC, 1, rue Laurent Fries, BP 163, 67404 Illkirch, France.
J Med Chem. 1998 May 21;41(11):1803-14. doi: 10.1021/jm970406v.
On the basis of the recently determined crystal structures of the ligand binding domains (LBDs) of the retinoic acid nuclear receptors (NRs), we present a three-dimensional (3D) molecular model of the human estrogen receptor alpha (hERalpha) LBD. A literature search for mutants affecting the binding properties has been performed; 45 out of 48 published mutants can be explained satisfactorily on the basis of the model. Estradiol has been docked into the binding pocket to probe its interactions with the protein. Energy minimizations and molecular dynamics calculations were performed for various ligand orientations. To evaluate their quality, the different models were scored using known structure-activity relationship (SAR) data for selected close estradiol homologues. The two best models explain largely the binding affinities of more distantly related ligands.
基于最近确定的视黄酸核受体（NRs）配体结合域（LBDs）的晶体结构，我们提出了人雌激素受体α（hERα）LBD的三维（3D）分子模型。我们对影响结合特性的突变体进行了文献检索；已发表的48个突变体中有45个可以基于该模型得到满意的解释。已将雌二醇对接至结合口袋中，以探究其与蛋白质的相互作用。对各种配体取向进行了能量最小化和分子动力学计算。为了评估不同模型的质量，使用选定的紧密雌二醇同系物的已知构效关系（SAR）数据对不同模型进行了评分。两个最佳模型在很大程度上解释了关系更远的配体的结合亲和力。
