The NOESY JIGSAW: Automated protein secondary structure and main-chain assignment from sparse, unassigned NMR data
The NOESY JIGSAW: Automated protein secondary structure and main-chain assignment from sparse, unassigned NMR data
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DOI：
10.1089/106652700750050934
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发表时间：
2000-01-01
影响因子：
1.7
通讯作者：
Donald, BR
中科院分区：
文献类型：
--
作者：
Bailey-Kellogg, C;Widge, A;Donald, BR
为了以与当前基因测序技术相当的速度评估基因的结构和功能的蛋白质产物，需要结构基因组学（或蛋白质组学）的高通量，数据导向的计算协议。JIGSAW算法是一种新型的高通量、自动化的核磁共振蛋白质结构表征方法，JIGSAW应用图算法和概率推理技术，强制执行第一原理一致性规则，以克服5-10%的信噪比，它由两个主要组成部分组成：(1)基于图的非赋值异核磁共振数据二级结构模式识别；(2)通过对已识别的二级结构元素与主序列的概率比对来赋值光谱峰。延迟分配消除了传统方法面临的瓶颈，传统方法首先将数十个实验中的峰值关联起来。JIGSAW只使用了4个实验，每个实验都不需要c -13标记的蛋白质，从而大大减少了湿实验室分子生物学的数量和费用以及总光谱仪时间。三个测试蛋白质的结果表明，JIGSAW正确识别了79-100%的α -螺旋和46-65%的β -片NOE连接，并正确排列了33-100%的二级结构元件。JIGSAW非常快，在pentium级Linux工作站上运行几分钟即可完成。这种方法产生快速且相当精确的结构计算（与传统的缓慢且极其精确的结构计算相反）。它可以用于快速结构分析，以便在调查早期将数据快速传递给生物学家，并且原则上可以以类似自动化的方式应用于大部分蛋白质组。
High-throughput, data-directed computational protocols for Structural Genomics (or Proteomics) are required in order to evaluate the protein products of genes for structure and function at rates comparable to current gene-sequencing technology. This paper presents the JIGSAW algorithm, a novel high-throughput, automated approach to protein structure characterization with nuclear magnetic resonance (NMR), JIGSAW applies graph algorithms and probabilistic reasoning techniques, enforcing first-principles consistency rules in order to overcome a 5-10% signal-to-noise ratio, It consists of two main components: (1) graph-based secondary structure pattern identification in unassigned heteronuclear NMR data, and (2) assignment of spectral peaks by probabilstic alignment of identified secondary structure elements against the primary sequence. Deferring assignment eliminates the bottleneck faced by traditional approaches, which begin by correlating peaks among dozens of experiments. JIGSAW utilizes only four experiments, none of which requires C-13-labeled protein, thus dramatically reducing both the amount and expense of wet lab molecular biology and the total spectrometer time, Results for three test proteins demonstrate that JIGSAW correctly identifies 79-100% of alpha -helical and 46-65% of beta -sheet NOE connectivities and correctly aligns 33-100% of secondary structure elements. JIGSAW is very fast, running in minutes on a Pentium-class Linux workstation, This approach yields quick and reasonably accurate (as opposed to the traditional slow and extremely accurate) structure calculations. It could be useful for quick structural assays to speed data to the biologist early in an investigation and could in principle be applied in an automation-like fashion to a large fraction of the proteome.