Morphological similarity: A 3D molecular similarity method correlated with protein-ligand recognition
Morphological similarity: A 3D molecular similarity method correlated with protein-ligand recognition
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DOI：
10.1023/a:1008100132405
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发表时间：
2000-02-01
影响因子：
3.5
通讯作者：
Jain, AN
中科院分区：
文献类型：
--
作者：
Jain, AN
蛋白质对小分子的识别依赖于三维分子表面的互补性。然而，分析小分子相似性的主要技术是基于二维化学结构，在生物活性相关性的并排比较中，此类技术通常优于三维技术。本文介绍了一种新的分子相似性方法，称为形态相似性（MS），它解决了明显的悖论。从晶体学上已知其蛋白质结合状态的一组配体中鉴定出两组分子对。结合相同蛋白质位点的对形成第一组，结合不同位点的对形成第二组。结果表明，MS 能够比基准 2D 相似性技术更好地分离这两个集合。此外，MS 与结合配体状态的晶体学观察一致，与结合状态的信息无关。 MS 计算效率高，可实际应用于大型化合物库。
Recognition of small molecules by proteins depends on three-dimensional molecular surface complementarity. However, the dominant techniques for analyzing the similarity of small molecules are based on two-dimensional chemical structure, with such techniques often outperforming three-dimensional techniques in side-by-side comparisons of correlation to biological activity. This paper introduces a new molecular similarity method, termed morphological similarity (MS), that addresses the apparent paradox. Two sets of molecule pairs are identified from a set of ligands whose protein-bound states are known crystallographically. Pairs that bind the same protein sites form the first set, and pairs that bind different sites form the second. MS is shown to separate the two sets significantly better than a benchmark 2D similarity technique. Further, MS agrees with crystallographic observation of bound ligand states, independent of information about bound states. MS is efficient to compute and can be practically applied to large libraries of compounds.