M-TASSER: An algorithm for protein quaternary structure prediction
M-TASSER: An algorithm for protein quaternary structure prediction
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DOI：
10.1529/biophysj.107.114280
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发表时间：
2008-02-01
影响因子：
3.4
通讯作者：
Skolnick, Jeffrey
中科院分区：
文献类型：
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作者：
Chen, Huiling;Skolnick, Jeffrey
据估计，在一个细胞中，每个蛋白质平均与大约10个其他蛋白质相互作用，导致成千上万的蛋白质已知或怀疑有相互作用伙伴;其中只有一小部分已经解决了蛋白质结构。为了部分解决这个问题，我们开发了M-TASSER，一种从序列中预测蛋白质四级结构的分层方法，该方法涉及通过多聚体线程进行模板识别，然后进行多聚体模型组装和细化。最后通过结构聚类的方法对模型进行选择。M-TASSER已经在二聚体文库中包含241个具有弱序列相似性模板的二聚体和246个没有多聚体模板的二聚体的基准组上进行了测试。在预测作为二聚体相互作用的总共207个靶标中，165个（80%）被正确地指定为相互作用，真阳性率为68%，假阳性率为17%。对于单体、界面和二聚体结构，初始最佳模板结构在圆上具有与天然的5.3、6.7和7.4（A）的平均均方根偏差。最终的模型显示，对于单体、界面和二聚体结构，在初始模板结构上，平均均方根偏差改善为1.3、1.3和1.5（A），其中87%的情况下明显细化。因此，我们开发了一种有前途的方法来预测与已解析四级结构的蛋白质具有弱序列相似性的蛋白质的全长四级结构。
In a cell, it has been estimated that each protein on average interacts with roughly 10 others, resulting in tens of thousands of proteins known or suspected to have interaction partners; of these, only a tiny fraction have solved protein structures. To partially address this problem, we have developed M-TASSER, a hierarchical method to predict protein quaternary structure from sequence that involves template identification by multimeric threading, followed by multimer model assembly and refinement. The final models are selected by structure clustering. M-TASSER has been tested on a benchmark set comprising 241 dimers having templates with weak sequence similarity and 246 without multimeric templates in the dimer library. Of the total of 207 targets predicted to interact as dimers, 165 (80%) were correctly assigned as interacting with a true positive rate of 68% and a false positive rate of 17%. The initial best template structures have an average root mean-square deviation to native of 5.3, 6.7, and 7.4 (A) over circle for the monomer, interface, and dimer structures. The final model shows on average a root mean-square deviation improvement of 1.3, 1.3, and 1.5 (A) over circle over the initial template structure for the monomer, interface, and dimer structures, with refinement evident for 87% of the cases. Thus, we have developed a promising approach to predict full-length quaternary structure for proteins that have weak sequence similarity to proteins of solved quaternary structure.