Addressing the intrinsic disorder bottleneck in structural proteomics
Addressing the intrinsic disorder bottleneck in structural proteomics
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DOI：
10.1002/prot.20446
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发表时间：
2005-05-15
影响因子：
2.9
通讯作者：
Markley, JL
中科院分区：
文献类型：
--
作者：
Oldfield, CJ;Ulrich, EL;Markley, JL
真核结构基因组学中心（CESG），作为蛋白质结构计划（PSI）的一部分，已经建立了一个高通量的真核蛋白结构测定管道。核磁共振波谱是这个管道的一个组成部分，既可以作为结构确定的方法，也可以作为筛选蛋白质稳定结构的手段。由于计算方法估计许多真核蛋白是高度无序的，大约在项目开始1年后，CESG开始使用一种算法（自然无序区域预测器，PONDR (R)）来避免可能无序的蛋白质。我们报告了一个回顾性分析的影响，这种过滤的产量可行的结构确定候选人。此外，我们还利用我们现有的数据库对拟南芥（Arabidopsis thaliana）和秀丽隐杆线虫（Caenorhabditis elegans）的70个蛋白靶点进行了结果分析，这些蛋白靶点被统一标记为氮-15，并通过NMR波谱进行了无序筛选，将原始算法与其他13种预测序列无序的方法进行了比较。我们的研究表明，通过选择提供最佳性能的算法去除预测紊乱的靶标，可以显著提高真核生物结构蛋白质组学的效率。(c) 2005 Wiley-Liss, Inc。
The Center for Eukaryotic Structural Genomics (CESG), as part of the Protein Structure Initiative (PSI), has established a high-throughput structure determination pipeline focused on eukaryotic proteins. NMR spectroscopy is an integral part of this pipeline, both as a method for structure determinations and as a means for screening proteins for stable structure. Because computational approaches have estimated that many eukaryotic proteins are highly disordered, about 1 year into the project, CESG began to use an algorithm (the Predictor of Naturally Disordered Regions, PONDR (R)) to avoid proteins that were likely to be disordered. We report a retrospective analysis of the effect of this filtering on the yield of viable structure determination candidates. In addition, we have used our current database of results on 70 protein targets from Arabidopsis thaliana and 1 from Caenorhabditis elegans, which were labeled uniformly with nitrogen-15 and screened for disorder by NMR spectroscopy, to compare the original algorithm with 13 other approaches for predicting disorder from sequence. Our study indicates that the efficiency of structural proteomics of eukaryotes can be improved significantly by removing targets predicted to be disordered by an algorithm chosen to provide optimal performance. (c) 2005 Wiley-Liss, Inc.