Direct-Coupling Analysis of nucleotide coevolution facilitates RNA secondary and tertiary structure prediction.
Direct-Coupling Analysis of nucleotide coevolution facilitates RNA secondary and tertiary structure prediction.
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DOI：
10.1093/nar/gkv932
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发表时间：
2015-12-02
影响因子：
14.9
通讯作者：
Weigt M
中科院分区：
文献类型：
--
作者：
De Leonardis E;Lutz B;Ratz S;Cocco S;Monasson R;Schug A;Weigt M
尽管非编码RNA具有生物学重要性，但其结构表征仍然具有挑战性。利用快速增长的序列数据库，我们分析核苷酸的同源序列之间的协同进化，通过直接耦合分析，以检测核苷酸-核苷酸接触。对于一组有代表性的核糖开关，我们表明，直接耦合分析的结果与广义Nussinov算法相结合，系统地提高了RNA二级结构预测的结果，超越了传统的协方差方法的基础上的互信息。更重要的是，我们表明，直接耦合分析的结果是丰富的三级结构接触。通过将这些预测整合到分子建模工具中，与单独使用二级结构信息相比，可以获得系统改进的三级结构预测。
Despite the biological importance of non-coding RNA, their structural characterization remains challenging. Making use of the rapidly growing sequence databases, we analyze nucleotide coevolution across homologous sequences via Direct-Coupling Analysis to detect nucleotide-nucleotide contacts. For a representative set of riboswitches, we show that the results of Direct-Coupling Analysis in combination with a generalized Nussinov algorithm systematically improve the results of RNA secondary structure prediction beyond traditional covariance approaches based on mutual information. Even more importantly, we show that the results of Direct-Coupling Analysis are enriched in tertiary structure contacts. By integrating these predictions into molecular modeling tools, systematically improved tertiary structure predictions can be obtained, as compared to using secondary structure information alone.