Automated structure-based prediction of functional sites in proteins: Applications to assessing the validity of inheriting protein function from homology in genome annotation and to protein docking
Automated structure-based prediction of functional sites in proteins: Applications to assessing the validity of inheriting protein function from homology in genome annotation and to protein docking
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DOI：
10.1006/jmbi.2001.4870
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发表时间：
2001-08-10
影响因子：
5.6
通讯作者：
Sternberg, MJE
中科院分区：
文献类型：
--
作者：
Aloy, P;Querol, E;Sternberg, MJE
基因组注释中的一个主要问题是将功能从特征蛋白转移到未知活性的同源物是否有效。在这里，我们表明人们可以采用一种策略，使用基于结构的蛋白质功能位点预测来评估功能遗传的可靠性。我们已经在进化跟踪方法的基础上对方法进行了自动化和基准测试。使用多序列比对，我们确定了不变的极性残基，然后将其映射到蛋白质结构上。这些不变残基的空间簇形成了预测的功能位点。对于86种被检测的蛋白质中的68种，该方法获得了观察到的功能位点的信息。该算法用于功能位点预测，然后评估在同源物之间转移功能的有效性。该方法对18对功能不相关的同源蛋白和70对功能相关的同源蛋白进行了检测，准确率达94%。这种自动化方法可以连接到基因组注释方案。最后，我们研究了功能位点预测在蛋白质-蛋白质和蛋白质- dna对接中的应用。预测功能位点的使用被证明可以过滤假定的对接复合物，其辨别类似于通过手动包括有关活性位点或dna结合残基的生物信息获得的辨别。(C) 2001学术出版社。
A major problem in genome annotation is whether it is valid to transfer the function from a characterised protein to a homologue of unknown activity. Here, we show that one can employ a strategy that uses a structure-based prediction of protein functional sites to assess the reliability of functional inheritance. We have automated and benchmarked a method based on the evolutionary trace approach. Using a multiple sequence alignment, we identified invariant polar residues, which were then mapped onto the protein structure. Spatial clusters of these invariant residues formed the predicted functional site. For 68 of 86 proteins examined, the method yielded information about the observed functional site. This algorithm for functional site prediction was then used to assess the validity of transferring the function between homologues. This procedure was tested on 18 pairs of homologous proteins with unrelated function and 70 pairs of proteins with related function, and was shown to be 94% accurate. This automated method could be linked to schemes for genome annotation. Finally, we examined the use of functional site prediction in protein-protein and protein-DNA docking. The use of predicted functional sites was shown to filter putative docked complexes with a discrimination similar to that obtained by manually including biological information about active sites or DNA-binding residues. (C) 2001 Academic Press.