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Multiple Graph Alignment for the Structural Analysis of Protein Active Sites

机译:蛋白质活性位点结构分析的多图比对

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摘要

Graphs are frequently used to describe the geometry and also the physicochemical composition of protein active sites. Here, the concept of graph alignment as a novel method for the structural analysis of protein binding pockets is presented. Using inexact graph-matching techniques, one is able to identify both conserved areas and regions of difference among different binding pockets. Thus, using multiple graph alignments, it is possible to characterize functional protein families and to examine differences among related protein families independent of sequence or fold homology. Optimized algorithms are described for the efficient calculation of multiple graph alignments for the analysis of physicochemical descriptors representing protein binding pockets. Additionally, it is shown how the calculated graph alignments can be analyzed to identify structural features that are characteristic for a given protein family and also features that are discriminative among related families. The methods are applied to a substantial high-quality subset of the PDB database and their ability to successfully characterize and classify 10 highly populated functional protein families is shown. Additionally, two related protein families from the group of serine proteases are examined and important structural differences are detected automatically and efficiently.
机译:图形通常用于描述蛋白质活性位点的几何形状以及理化组成。在这里,提出了图对齐的概念,将其作为蛋白质结合口袋结构分析的一种新方法。使用不精确的图匹配技术,可以识别不同结合口袋之间的保守区域和差异区域。因此,使用多个图比对,有可能表征功能性蛋白家族并检查独立于序列或折叠同源性的相关蛋白家族之间的差异。描述了用于有效计算多个图比对的优化算法,以分析代表蛋白质结合袋的理化描述符。此外,它还显示了如何分析计算的图谱比对,以鉴定给定蛋白质家族的特征性结构特征以及相关家族之间的区别性特征。将该方法应用于PDB数据库的大量高质量子集,并显示了它们成功地表征和分类10个高种群功能蛋白家族的能力。另外,检查了来自丝氨酸蛋白酶组的两个相关蛋白家族,并自动和有效地检测到重要的结构差异。

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