RNA-PAIRS: RNA probabilistic assignment of imino resonance shifts
RNA-PAIRS: RNA probabilistic assignment of imino resonance shifts
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DOI：
10.1007/s10858-012-9603-z
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发表时间：
2012-04-01
影响因子：
2.7
通讯作者：
Eghbalnia, Hamid R.
中科院分区：
文献类型：
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作者：
Bahrami, Arash;Clos, Lawrence J., II;Eghbalnia, Hamid R.
RNA的重要生物学作用进一步突出了提高研究RNA结构和功能的方法的准确性、效率和范围的需要。核磁共振（NMR）光谱是至关重要的，因为它的独特功能，以促进RNA结构生物学的目标。然而，在RNA的NMR光谱中的分散模式使得自动化共振分配，在生物分子的NMR研究的关键步骤，显着的挑战。在这里，我们提出了RNA概率分配的亚氨基共振位移（RNA-PAIRS），一种自动分配RNA亚氨基共振的方法，同步验证和校正预测的二级结构。RNA-PAIRS代表了分配模式建模的一个进步，因为它同时从一开始就为实验NMR数据的分配和预测RNA二级结构的概率网络提供了种子。随后，RNA-PAIRS启动了一个动态网络，在预测和实验证据之间产生反响，以协调和纠正共振分配和二级结构信息。当赋值和碱基配对被认为与观察到的串扰最一致时，该过程停止。RNA-PAIRS的当前实现使用来自质子-氮杂波多量子相关（H-1-N-15 2D HMQC）和质子-质子核奥弗豪泽增强光谱（H-1-H-1 2D NOESY）实验的初始峰列表。我们已经评估了RNA-PAIRS的性能，通过使用它来分析来自26个先前研究的RNA的NMR数据集，包括111个核苷酸的复合物。对于中等大小的RNA分子，在一系列相对复杂的结构基序上，平均分配准确率超过90%，而平均碱基对预测准确率超过93%。RNA-PAIRS产生了准确的分配和碱基配对，与大多数NMR共振的亚氨基共振一致，即使最初的预测只有适度的准确性。RNA-PAIRS作为公共网络服务器可在http://pine.nmrfam.wisc.edu/RNA/上获得。
The significant biological role of RNA has further highlighted the need for improving the accuracy, efficiency and the reach of methods for investigating RNA structure and function. Nuclear magnetic resonance (NMR) spectroscopy is vital to furthering the goals of RNA structural biology because of its distinctive capabilities. However, the dispersion pattern in the NMR spectra of RNA makes automated resonance assignment, a key step in NMR investigation of biomolecules, remarkably challenging. Herein we present RNA Probabilistic Assignment of Imino Resonance Shifts (RNA-PAIRS), a method for the automated assignment of RNA imino resonances with synchronized verification and correction of predicted secondary structure. RNA-PAIRS represents an advance in modeling the assignment paradigm because it seeds the probabilistic network for assignment with experimental NMR data, and predicted RNA secondary structure, simultaneously and from the start. Subsequently, RNA-PAIRS sets in motion a dynamic network that reverberates between predictions and experimental evidence in order to reconcile and rectify resonance assignments and secondary structure information. The procedure is halted when assignments and base-parings are deemed to be most consistent with observed crosspeaks. The current implementation of RNA-PAIRS uses an initial peak list derived from proton-nitrogen heteronuclear multiple quantum correlation (H-1-N-15 2D HMQC) and proton-proton nuclear Overhauser enhancement spectroscopy (H-1-H-1 2D NOESY) experiments. We have evaluated the performance of RNA-PAIRS by using it to analyze NMR datasets from 26 previously studied RNAs, including a 111-nucleotide complex. For moderately sized RNA molecules, and over a range of comparatively complex structural motifs, the average assignment accuracy exceeds 90%, while the average base pair prediction accuracy exceeded 93%. RNA-PAIRS yielded accurate assignments and base pairings consistent with imino resonances for a majority of the NMR resonances, even when the initial predictions are only modestly accurate. RNA-PAIRS is available as a public web-server at http://pine.nmrfam.wisc.edu/RNA/.