Analysis of evolutionary conservation patterns and their influence on identifying protein functional sites
Analysis of evolutionary conservation patterns and their influence on identifying protein functional sites
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DOI：
10.1142/s0219720014400034
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发表时间：
2014-10-01
影响因子：
1
通讯作者：
Yamana, Hayato
中科院分区：
文献类型：
--
作者：
Fang, Chun;Noguchi, Tamotsu;Yamana, Hayato
位置特异性评分矩阵（PSSM）中包含的进化保守信息已被基于序列的方法广泛用于识别蛋白质功能位点，因为所有功能位点，无论是有序还是无序的蛋白质，都在一定程度上被发现是保守的。然而，不同的功能位点有不同的保守模式，其中一些是线性的上下文，其中一些是混合的高度可变的残基，和其他一些似乎是独立的保守。PSSM中的每个值彼此独立地计算，而不携带序列中残基的上下文信息。因此，采用PSSM的直接输出进行预测，未能考虑PSSM中残基保守模式与保守评分分布之间的关系。为了证明结合PSSM与功能位点的特定保守模式进行预测的重要性，分析了三种不同的基于PSSM的方法来识别三种功能位点。结果表明，不同的PSSM为基础的方法在他们的能力不同，以确定不同的模式的功能位点，更好地结合PSSM与特定的残基保守模式将在很大程度上促进预测。
Evolutionary conservation information included in position-specific scoring matrix (PSSM) has been widely adopted by sequence-based methods for identifying protein functional sites, because all functional sites, whether in ordered or disordered proteins, are found to be conserved at some extent. However, different functional sites have different conservation patterns, some of them are linear contextual, some of them are mingled with highly variable residues, and some others seem to be conserved independently. Every value in PSSMs is calculated independently of each other, without carrying the contextual information of residues in the sequence. Therefore, adopting the direct output of PSSM for prediction fails to consider the relationship between conservation patterns of residues and the distribution of conservation scores in PSSMs. In order to demonstrate the importance of combining PSSMs with the specific conservation patterns of functional sites for prediction, three different PSSM-based methods for identifying three kinds of functional sites have been analyzed. Results suggest that, different PSSM-based methods differ in their capability to identify different patterns of functional sites, and better combining PSSMs with the specific conservation patterns of residues would largely facilitate the prediction.