RNA 3D structure prediction guided by independent folding of homologous sequences
RNA 3D structure prediction guided by independent folding of homologous sequences
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DOI：
10.1186/s12859-019-3120-y
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发表时间：
2019-10-22
影响因子：
3
通讯作者：
Bujnicki, Janusz M.
中科院分区：
文献类型：
--
作者：
Magnus, Marcin;Kappel, Kalli;Bujnicki, Janusz M.
背景近年来，对RNA重要性的理解发生了巨大变化。与蛋白质一样，RNA分子的功能由其三级结构编码，而三级结构又由分子序列决定。复杂RNA的三级结构预测仍然是一个具有挑战性的任务。结果使用观察到的RNA序列从相同的RNA家族折叠成保守的结构，我们在这里测试是否可以提高从头RNA结构预测的RNA同源物的并行建模。EvoClustRNA是一个多步建模过程，其中使用Rfam数据库选择靶序列的同源序列。随后，使用Rosetta FARFAR和SimRNA进行独立的折叠模拟。基于常见螺旋片段的最常见结构排列来选择靶序列的模型。作为测试，在两个盲RNA谜题挑战中，EvoClustRNA预测在所有提交的L-谷氨酰胺核糖开关中排名第一，在ZMP核糖开关中排名第二。此外，通过已知结构的基准，我们发现了几种情况下，其中特定的同源物是不寻常的服从结构恢复折叠模拟相比，单一的原始目标序列。结论本工作首次证明了从RNA家族比对中选择靶序列对RNA三维结构预测的重要性。这些观察结果促使人们研究一个新的研究方向，即检查相关RNA序列的3D结构“可折叠性”或“可预测性”，以获得准确的预测。为了支持这一领域的新研究，我们以文档化和随时可用的形式提供所有相关脚本。通过探索新的想法和识别当前RNA 3D结构预测方法的局限性，这项工作使我们更接近于接近原生的计算RNA 3D模型。
Background The understanding of the importance of RNA has dramatically changed over recent years. As in the case of proteins, the function of an RNA molecule is encoded in its tertiary structure, which in turn is determined by the molecule's sequence. The prediction of tertiary structures of complex RNAs is still a challenging task. Results Using the observation that RNA sequences from the same RNA family fold into conserved structure, we test herein whether parallel modeling of RNA homologs can improve ab initio RNA structure prediction. EvoClustRNA is a multi-step modeling process, in which homologous sequences for the target sequence are selected using the Rfam database. Subsequently, independent folding simulations using Rosetta FARFAR and SimRNA are carried out. The model of the target sequence is selected based on the most common structural arrangement of the common helical fragments. As a test, on two blind RNA-Puzzles challenges, EvoClustRNA predictions ranked as the first of all submissions for the L-glutamine riboswitch and as the second for the ZMP riboswitch. Moreover, through a benchmark of known structures, we discovered several cases in which particular homologs were unusually amenable to structure recovery in folding simulations compared to the single original target sequence. Conclusion This work, for the first time to our knowledge, demonstrates the importance of the selection of the target sequence from an alignment of an RNA family for the success of RNA 3D structure prediction. These observations prompt investigations into a new direction of research for checking 3D structure "foldability" or "predictability" of related RNA sequences to obtain accurate predictions. To support new research in this area, we provide all relevant scripts in a documented and ready-to-use form. By exploring new ideas and identifying limitations of the current RNA 3D structure prediction methods, this work is bringing us closer to the near-native computational RNA 3D models.