Comparative protein structure modeling by combining multiple templates and optimizing sequence-to-structure alignments
Comparative protein structure modeling by combining multiple templates and optimizing sequence-to-structure alignments
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DOI：
10.1093/bioinformatics/btm377
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发表时间：
2007-10-01
期刊：
影响因子：
5.8
通讯作者：
Fiser, Andras
中科院分区：
文献类型：
--
作者：
Fernandez-Fuentes, Narcis;Rai, Brajesh K.;Fiser, Andras
动机：推进比较蛋白质结构建模的两个主要瓶颈是多个模板结构的有效组合和生成正确的输入目标-模板对齐。结果：提出了一种基于多模板的多映射方法（Multiple Mapping method with Multiple Templates, M4T），该方法实现了多模板结构（MT）的自动选择和组合算法以及对齐优化协议（Multiple Mapping method， MMM）。M4T的MT模块通过迭代聚类方法选择和组合多个模板结构，该方法考虑到每个模板的“独特”贡献，它们之间的序列相似性以及与目标序列的相似性以及它们的实验分辨率。MMM是一种序列到结构的对齐方法，它根据模板结构的结构环境中的拟合程度，将可选择对齐的区域进行最优组合。得到的M4T对齐用作比较建模模块的输入。M4T的性能已经在CASP6比较建模目标序列和更大的独立测试集上进行了基准测试，并显示出较当前最先进方法的良好性能。
Motivation: Two major bottlenecks in advancing comparative protein structure modeling are the efficient combination of multiple template structures and the generation of a correct input target-template alignment.Results: A novel method, Multiple Mapping Method with Multiple Templates (M4T) is introduced that implements an algorithm to automatically select and combine Multiple Template structures (MT) and an alignment optimization protocol (Multiple Mapping Method, MMM). The MT module of M4T selects and combines multiple template structures through an iterative clustering approach that takes into account the 'unique' contribution of each template, their sequence similarity among themselves and to the target sequence, and their experimental resolution. MMM is a sequence-to-structure alignment method that optimally combines alternatively aligned regions according to their fit in the structural environment of the template structure. The resulting M4T alignment is used as input to a comparative modeling module. The performance of M4T has been benchmarked on CASP6 comparative modeling target sequences and on a larger independent test set, and showed favorable performance to current state of the art methods.