3D-QSAR and docking studies of estrogen compounds based on estrogen receptor beta

作者：Yang XuShu; Wang XiaoDong^*; Luo Si; Ji Li; Qin Liang; Li Rong; Sun Cheng; Wang LianSheng

来源：Science in China Series B-Chemistry, 2009, 52(7): 1042-1050.

DOI：10.1007/s11426-009-0068-1

• estrogen receptor beta
• 3D-QSAR
• docking
• comparative molecular similarity indices analysis (CoMSIA)
• prediction for activity
• molecular mechanisms

Close attention has been paid to estrogen compounds because these chemicals may pose a serious threat to the health of humans and wildlife. Estrogen receptor (ER) exists as two subtypes, ER alpha and ER beta. The difference in amino acids sequence of the binding sites of ER alpha and ER beta might lead to a result that some synthetic estrogens and naturally occurring steroidal ligands have different relative affinities and binding modes for ER alpha and ER beta. In this investigation, comparative molecular similarity indices analysis (CoMSIA) was performed on 50 estrogen compounds binding ER beta to find out the structural relationship with the activities. We also compared two alignment schemes employed in CoMSIA analysis, namely, atom-fit and receptor-based alignment, with respect to the predictive capability of their respective models for structurally diverse data sets. The model with the significant correlation and the best predictive power (R (2)=0.961, q (LOO) (2) =0.671, R (Pred) (2) =0.722) was achieved. The CoMSIA and docking results revealed the structural features related to an activity and provided an insight into molecular mechanisms of estrogenic activities for estrogen compounds.

• 出版日期2009-7
• 单位南京大学