两类促肾上腺皮质释放激素（CRH）拮抗剂的分子场分析

Molecular Field Analysis of Two Sets of Non-Peptide Corticotropin-Releasing Hormone Antagonists

采用比较分子相似性指数分析方法(CoMSIA)及比较分子场分析方法(CoMFA)研究了两组CRH拮抗剂结构与活性的关系.在两种方法中,都考虑了静电场、立体场以及氢键场对构效关系的影响,结果表明采用CoMSIA得到构效关系模型要明显优于采用CoMFA得到的构效关系模型.在CoMSIA计算中,当引入疏水场时,三维构效关系模型能得到明显的改善,通过这个三维构效关系模型,可以较为精确地预测化合物的活性.通过分析分子场等值面图在空间的分布,可以观察到叠合分子周围的立体、静电以及疏水特征对化合物活性的影响.

The quantitative structural activity relationship of two sets of non - peptide corticotropin - releasing hormone antagonists were performed by using two kinds of 3D - QSAR approaches: comparative molecular similarity indices analysis (CoMSIA) and comparative molecular field analysis (CoMFA). Three kinds of molecular fields, including electrostatic field, steric field and H - bond fields, were considered in CoMSIA and CoMFA calculations. The computed results show that the 3D - QSAR models from CoMSIA. are obviously superior to those from CoMFA. In CoMSIA calculations, the addition of the hydrophobic field could significantly improve the obtained 3D - QSAR model. From the analysis of the contour of the molecular field in the three dimensional space, the key features vital to ligand binding, including steric, electrostatic and hydrophobic properties, were identified, which were very important for us to trace these properties that really matter and take insight into the potential mechanisms of intermolecular interactions between antagonists and receptor.