Artymiuk P J, Poirrette A R, Grindley H M, Rice D W, Willett P
Krebs Institute for Biomolecular Research Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, U.K.
J Mol Biol. 1994 Oct 21;243(2):327-44. doi: 10.1006/jmbi.1994.1657.
This paper discusses the use of graph-theoretic methods for the representation and searching of three-dimensional patterns of side-chains in protein structures. The position of a side-chain is represented by pseudo-atoms, and the relative positions of pairs of side-chains by the distances between them. This description of the geometry can be represented by a labelled graph in which the nodes and the edges of the graph represent the pseudo-atoms and the sets of inter-pseudo-atomic distances, respectively. Given such a representation, a protein can be searched for the presence of a user-defined query pattern of side-chains by means of a subgraph-isomorphism algorithm which is implemented in the program ASSAM. Experiments with one such algorithm, that due to Ullmann, show that it provides both an effective and a highly efficient way of searching for patterns of side-chains. The method is illustrated by searches for the serine protease catalytic triad, for residues involved in the catalytic activity of staphyloccocal nuclease, and for the zinc-binding side-chains of thermolysin. The catalytic triad pattern search revealed the existence of a second Asp-His-Ser triad-like arrangement of residues in trypsinogen and chymotrypsinogen, in addition to the catalytic residues. In addition the program can be used to search for hypothetical patterns, as is shown for a pattern of three tryptophan side-chains. These searches demonstrate that the search algorithm can successfully retrieve the great majority of the expected proteins, as well as other, previously unreported proteins that contain the pattern of interest.
本文讨论了使用图论方法来表示和搜索蛋白质结构中侧链的三维模式。侧链的位置由伪原子表示，侧链对之间的相对位置由它们之间的距离表示。这种几何描述可以由一个带标签的图来表示，其中图的节点和边分别表示伪原子和伪原子间距离的集合。给定这样一种表示形式，就可以通过在ASSAM程序中实现的子图同构算法，在蛋白质中搜索用户定义的侧链查询模式。使用其中一种算法（即乌尔曼算法）进行的实验表明，它为搜索侧链模式提供了一种有效且高效的方法。通过搜索丝氨酸蛋白酶催化三联体、葡萄球菌核酸酶催化活性相关的残基以及嗜热菌蛋白酶的锌结合侧链，对该方法进行了说明。催化三联体模式搜索揭示，除了催化残基外，在胰蛋白酶原和胰凝乳蛋白酶原中还存在第二种类似天冬氨酸 - 组氨酸 - 丝氨酸三联体的残基排列。此外，该程序还可用于搜索假设模式，如对三个色氨酸侧链模式的搜索所示。这些搜索表明，搜索算法能够成功检索出绝大多数预期的蛋白质，以及其他含有目标模式但此前未报道过的蛋白质。
