RNAs fold into distinct molecular conformations that are often essential for their functions. Accurate structure modeling of complex RNA motifs, including ubiquitous non-canonical base pairs and pseudoknots, remains a challenge. Here, we present an NMR-guided all-atom discrete molecular dynamics (DMD) platform, iFoldNMR, for rapid and accurate structure modeling of complex RNAs. We show that sparse distance constraints from imino resonances, which can be readily obtained from routine NMR experiments and easier to compile than laborious assignments of non-solvent-exchangeable protons, are sufficient to direct a DMD search for low-energy RNA conformers. Benchmarking on a set of RNAs with complex folds spanning up to 56 nucleotides in length yields structural models that recapitulate experimentally determined structures with all-heavy-atom RMSDs ranging from 2.4 to 6.5 Å. This platform represents an efficient approach for high-throughput RNA structure modeling and will facilitate analysis of diverse, newly discovered functional RNAs.

中文翻译：

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使用稀疏NMR约束条件对RNA进行结构建模

RNA折叠成不同的分子构象，这对于它们的功能通常是必不可少的。复杂的RNA基序（包括无处不在的非规范碱基对和假结）的准确结构建模仍然是一个挑战。在这里，我们提出了NMR指导的全原子离散分子动力学（DMD）平台iFoldNMR，用于快速，准确地对复杂RNA进行结构建模。我们表明，来自亚氨基共振的稀疏距离限制（可以轻松地从常规NMR实验获得并且比非溶剂交换质子的辛苦分配更容易编译）足以指导DMD搜索低能RNA构象异构体。对一组复杂的，长度高达56个核苷酸的复杂折叠的RNA进行基准测试，可以得到结构模型，该模型可以概括实验确定的结构，其全重原子RMSD范围为2.4至6.5Å。该平台代表了一种高通量RNA结构建模的有效方法，将有助于分析各种新发现的功能性RNA。