维甲化合物与维甲X受体相互作用模拟及QSAR研究

Molecular Modeling and QSAR Studies on the Interaction Mechanism of Retinoids Binding to RXR

用分子对接确定了一系列RXR激动剂与受体的作用方式,与X衍射测得的晶体复合物中9-cis-RA的作用方式相近.对接后的配体-受体复和物经分子力学优化后更接近药效构象,两者相互作用能与活性具有一定的相关性,相关系数R2=O.64.用活性构象建立的CoMFA模型比低能构象建立的CoMFA模型有更高的可信度,其交叉验证相关系数q2=0.791,非交叉验证相关系数r2=0.988,绝对误差SE=0.099,F6,33=456.8.

Retinoid X receptors (RXRs) play a critical role in the regulation of many biological activities and their specific agonists, including oxime ligands, functionally activate both homodimer RXR : RXR and heterodimer RXR : PPAR, the later relates to insulin sensitization and has a potential application in the treatment of type U diabetes. Based on RXR and 9 - cis - EA complex crystallographic data, interaction between these compounds and RXR are simulated with DOCK 4.0. After minimizing each ligand - receptor complex, from resulting energy and activity an equation is deduced with the correlation coefficient R-2 = 0.64. Two CoMFA models are built and compared. One model originates from the ligand conformation extracted directly from complex, the other from energy - minimized ligands. The higher significance of the former than that of the later suggests that the conformation from induced fit of receptor be more reliable.