Protein structure alignment considering phenotypic plasticity
Protein structure alignment considering phenotypic plasticity
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DOI：
10.1093/bioinformatics/btn271
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发表时间：
2008-08-15
期刊：
影响因子：
5.8
通讯作者：
Zimmer, Ralf
中科院分区：
文献类型：
--
作者：
Csaba, Gergely;Birzele, Fabian;Zimmer, Ralf
动机：蛋白质结构比较显示了蛋白质和蛋白质家族的差异和相似性，有助于阐明蛋白质的序列和结构进化。尽管有许多方法可以对具有或不具有灵活性的蛋白质结构相似性进行评分，并根据其结构精确地排列蛋白质，但一种有意义的进化距离测量和排列方法仍然缺乏，这种方法可以在结构水平上模拟蛋白质序列中发生的突变，插入和缺失的成本。结果：本文引入了一种新的蛋白质结构相似性度量方法，并提出了一种称为表型可塑性方法（PPM）的新方法，该方法通过测量一种结构变形为另一种结构的成本，明确地试图在结构水平上模拟两种蛋白质的进化距离。PPM对蛋白质结构进行排列，考虑到在结构组中自然观察到的变化（表型可塑性），同时保留结构的整体拓扑排列。在两个基准集上，对比已知的结构分类方法，评估了PPM在检测蛋白质结构相似性方面的性能。更大的集合由来自SCOP数据库的360多万个结构对组成，这些结构对也在CATH中一致分类。在目前的参数化中，PPM已经根据各种评估标准在这两个集合上表现得与TM-Align和Vorolign等其他方法相当或更好，这表明该方法能够可靠地对已知蛋白质结构进行分类，检测它们的相似性并计算准确的排列，尽管表型可塑性。
Motivation: Protein structure comparison exhibits differences and similarities of proteins and protein families and may help to elucidate protein sequence and structure evolution. Despite many methods to score protein structure similarity with and without flexibility and to align proteins accurately based on their structures, a meaningful evolutionary distance measure and alignment method which models the cost of mutations, insertions and deletions occurring in protein sequences on the structure level is still missing.Results: Here, we introduce a new measure for protein structure similarity and propose a novel method called phenotypic plasticity method (PPM) which explicitly tries to model the evolutionary distance of two proteins on the structure level by measuring the cost of morphing one structure into the other one. PPM aligns protein structures taking variations naturally observed in groups of structures (phenotypic plasticity) into account while preserving the overall topological arrangement of the structures. The performance of PPM in detecting similarities between protein structures is evaluated against well-known structure classification methods on two benchmark sets. The larger set consists of more than 3.6 million structure pairs from the SCOP database which are also consistently classified in CATH. In the current parameterization, PPM already performs comparable or better than other methods such as TM-Align and Vorolign on those two sets according to various evaluation criteria showing that the method is able to reliably classify known protein structures, to detect their similarities and to compute accurate alignments despite phenotypic plasticity.