Poirrette A R, Willett P, Allen F H
Department of Information Studies, University of Sheffield, UK.
J Mol Graph. 1991 Dec;9(4):203-17. doi: 10.1016/0263-7855(91)80013-p.
This paper describes the use of generalized valence angles for the screening of pharmacophoric pattern searches in databases of three-dimensional chemical structures. A generalized valence angle is defined as the angle between two vectors, AB and BC, which have a common vertex B, and in which both vectors correspond to formal chemical bonds; one vector corresponds to a bond and the other to a non-bonded interaction; or both vectors correspond to non-bonded interactions. The screens are identified by a statistical analysis of the frequencies of occurrence of these angle-based features in the Cambridge Structural Database. The occurrence frequencies are discussed and shown to be explicable in terms of small, commonly occurring structural features. The effectiveness of the screens is demonstrated by an extensive series of searches for representative pharmacophoric patterns. The results are compared with those obtained from a similar series of searches using distance-based screens: The latter are found to give a better level of performance, and evidence is presented to suggest that this is due to a high degree of association between the assignments of the angle-based screens.
本文描述了广义价键角在三维化学结构数据库中筛选药效团模式搜索的应用。广义价键角定义为两个向量AB和BC之间的夹角，它们具有共同顶点B，且两个向量均对应于形式化学键；一个向量对应于一个键，另一个对应于非键相互作用；或者两个向量均对应于非键相互作用。通过对剑桥结构数据库中这些基于角度特征的出现频率进行统计分析来识别筛选条件。讨论了出现频率，并表明根据常见的小结构特征可以解释这些频率。通过对一系列代表性药效团模式的广泛搜索证明了筛选条件的有效性。将结果与使用基于距离的筛选条件进行的类似系列搜索所获得的结果进行比较：发现后者具有更好的性能水平，并且有证据表明这是由于基于角度的筛选条件的赋值之间存在高度相关性。
