Quantifying the similarities within fold space
Quantifying the similarities within fold space
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DOI：
10.1016/s0022-2836(02)00992-0
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发表时间：
2002-11-08
影响因子：
5.6
通讯作者：
Orengo, C
中科院分区：
文献类型：
--
作者：
Harrison, A;Pearl, F;Orengo, C
我们已经使用GRATH，一个基于图形的结构比较算法，映射在CATH域结构数据库中观察到的不同折叠之间的相似性。对倍数相似性分布的统计分析使我们能够评估任何相似性的显著性。因此，我们已经研究了是否最好将褶皱表示为离散实体，或者事实上，更准确的模型是否是连续体，其中褶皱通过共同的图案重叠。为了做到这一点，我们引入了一个新的统计措施的折叠相似性，称为合群。对于一个特定的褶皱，群居性测量有多少其他褶皱与该褶皱有显著的结构重叠，通常占较大结构的40%或更多。群聚褶皱通常包含超二级结构基序，如β-曲流、希腊钥匙、α-β辫状基序或α-发夹，它们与其他褶皱中的类似基序相匹配。除了一个例子之外，所有与数据库中20%或更多的其他折叠相匹配的最群居的折叠都是α-β蛋白。它们也出现在折叠空间的高度密集的结构区域，采用包含两层或多层α螺旋和β链的类β-螺旋排列。表现出低群居性的结构域是那些具有非常独特的折叠的结构域，具有很少的共同图案或以不寻常的排列包装的图案。大多数的超螺旋表现出低的群居性，尽管包含一些常见的超二级结构基序。在这些褶皱中，这些共同的图案以一种不寻常的方式组合在一起，代表了褶皱的一小部分（
We have used GRATH, a graph-based structure comparison algorithm, to map the similarities between the different folds observed in the CATH domain structure database. Statistical analysis of the distributions of the fold similarities has allowed us to assess the significance for any similarity. Therefore we have examined whether it is best to represent folds as discrete entities or whether, in fact, a more accurate model would be a continuum wherein folds overlap via common motifs. To do this we have introduced a new statistical measure of fold similarity, termed gregariousness. For a particular fold, gregariousness measures how many other folds have a significant structural overlap with that fold, typically comprising 40% or more of the larger structure. Gregarious folds often contain commonly occurring super-secondary structural motifs, such as beta-meanders, greek keys, alpha-beta plait motifs or alpha-hairpins, which are matching similar motifs in other folds. Apart from one example, all the most gregarious folds matching 20% or more of the other folds in the database, are alpha-beta proteins. They also occur in highly populated architectural regions of fold space, adopting sandwich-like arrangements containing two or more layers of alpha-helices and beta-strands.Domains that exhibit a low gregariousness, are those that have very distinctive folds, with few common motifs or motifs that are packed in unusual arrangements. Most of the superhelices exhibit low gregariousness despite containing some commonly occurring super-secondary structural motifs. In these folds, these common motifs are combined in an unusual way and represent a small proportion of the fold (