Belvisi L, Bravi G, Scolastico C, Vulpetti A, Salimbeni A, Todeschini R
Dipartimento di Chimica Organica e Industriale Centro del C.N.R., Milan, Italy.
J Comput Aided Mol Des. 1994 Apr;8(2):211-20. doi: 10.1007/BF00119868.
A 3D QSAR methodology based on the combined use of conformational analysis and chemometrics was applied to perform a comparative analysis of the 3D conformational features of 13 nonpeptide angiotensin II receptor antagonists showing different levels of binding affinity. Conformational analysis by using a molecular mechanics MM2 method was carried out for each of these structures to obtain conformational minima. These minima were described by ten interatomic distances which define the relative spatial disposition of five significant atoms belonging to relevant functional groups present in all the 13 molecules. The structure-activity relationship between the interatomic distances and the biological activity was then assessed by using chemometric methods (cluster analysis, principal component analysis, classification methods). With our indirect approach based on the search for geometrical similarity it was possible, even though structural information on the receptor active site was lacking, to identify the 3D geometrical requirements for the binding affinity of nonpeptide angiotensin II receptor inhibitors.
一种基于构象分析和化学计量学相结合的三维定量构效关系（3D QSAR）方法被用于对13种具有不同结合亲和力水平的非肽类血管紧张素II受体拮抗剂的三维构象特征进行比较分析。使用分子力学MM2方法对这些结构中的每一个进行构象分析，以获得构象极小值。这些极小值由十个原子间距离描述，这些距离定义了属于所有13个分子中相关官能团的五个重要原子的相对空间排布。然后使用化学计量学方法（聚类分析、主成分分析、分类方法）评估原子间距离与生物活性之间的构效关系。通过我们基于寻找几何相似性的间接方法，即使缺乏关于受体活性位点的结构信息，也能够确定非肽类血管紧张素II受体抑制剂结合亲和力的三维几何要求。
