Hidden conformations in protein structures
Hidden conformations in protein structures
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DOI：
10.1093/bioinformatics/btr292
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发表时间：
2011-07-15
期刊：
影响因子：
5.8
通讯作者：
Kliger, Yossef
中科院分区：
文献类型：
--
作者：
Ashkenazy, Haim;Unger, Ron;Kliger, Yossef
动机：预测蛋白质残基之间的相互作用（接触图预测）可以促进3D结构建模的各个方面。然而，从头接触预测的准确性仍然是有限的。随着结构基因组学计划的推进，同源蛋白质的解析结构可以用作多个模板，以改善未解析靶蛋白的主要构象的接触预测。此外，多个模板可以提供蛋白质构象空间的更宽视图。然而，成功地使用多个结构模板是不简单的，由于其变量的相关性的目标蛋白质，因为数据冗余issues.Results：我们在这里提出了一个算法，解决了这两个限制在使用多个结构模板。首先，该算法以承认多种构象的可能性的方式将从彼此共享高序列相似性的模板中提取的接触图联合起来。接下来，它将得到的联合图谱与它们与目标蛋白质的进化距离成反比。针对CASP 8目标测试该算法产生了高精度的接触图。值得注意的是，仅仅基于远程同源物的结构数据，我们的算法确定了残基-残基相互作用，这些相互作用解释了钙调蛋白（一种多方面的蛋白质）的所有已知构象。因此，采用多个模板，这提高了接触图的预测，也可以用来揭示新的构象。由于多个模板将很快可用于大多数蛋白质，我们的计划提出了一个有效的程序，他们的最佳考虑。
Motivation: Prediction of interactions between protein residues (contact map prediction) can facilitate various aspects of 3D structure modeling. However, the accuracy of ab initio contact prediction is still limited. As structural genomics initiatives move ahead, solved structures of homologous proteins can be used as multiple templates to improve contact prediction of the major conformation of an unsolved target protein. Furthermore, multiple templates may provide a wider view of the protein's conformational space. However, successful usage of multiple structural templates is not straightforward, due to their variable relevance to the target protein, and because of data redundancy issues.Results: We present here an algorithm that addresses these two limitations in the use of multiple structure templates. First, the algorithm unites contact maps extracted from templates sharing high sequence similarity with each other in a fashion that acknowledges the possibility of multiple conformations. Next, it weights the resulting united maps in inverse proportion to their evolutionary distance from the target protein. Testing this algorithm against CASP8 targets resulted in high precision contact maps. Remarkably, based solely on structural data of remote homologues, our algorithm identified residue-residue interactions that account for all the known conformations of calmodulin, a multifaceted protein. Therefore, employing multiple templates, which improves prediction of contact maps, can also be used to reveal novel conformations. As multiple templates will soon be available for most proteins, our scheme suggests an effective procedure for their optimal consideration.