Ab initio RNA folding by discrete molecular dynamics: From structure prediction to folding mechanisms
Ab initio RNA folding by discrete molecular dynamics: From structure prediction to folding mechanisms
复制标题
DOI：
10.1261/rna.894608
复制
发表时间：
2008-06-01
期刊：
影响因子：
4.5
通讯作者：
Dokholyan, Nikolay V.
中科院分区：
文献类型：
--
作者：
Ding, Feng;Sharma, Shantanu;Dokholyan, Nikolay V.
具有新功能的RNA分子重新引起了人们对精确预测RNA三维结构和折叠动力学的兴趣。然而，现有的方法在自动3D结构预测中效率低下。在这里，我们报告了一个强大的计算方法快速折叠的RNA分子。我们开发了一个简化的RNA模型的离散分子动力学（DMD）模拟，将碱基配对和碱基堆积的相互作用。我们证明了150个结构不同的RNA序列的正确折叠。大多数DMD预测的3D结构与实验结构的偏差< 4埃。对应于预测的三维结构的二级结构由94%的天然碱基对相互作用组成。折叠热力学和动力学的tRNA（苯丙氨酸），假结，和mRNA片段的DMD模拟与以前的实验结果一致。RNA分子的折叠以瞬时的、非天然的构象为特征，这表明非分级RNA折叠。我们的方法可以快速构象采样的RNA折叠，计算时间与RNA长度线性增加。我们设想这种方法作为一个有前途的工具，RNA的结构和功能分析。
RNA molecules with novel functions have revived interest in the accurate prediction of RNA three-dimensional (3D) structure and folding dynamics. However, existing methods are inefficient in automated 3D structure prediction. Here, we report a robust computational approach for rapid folding of RNA molecules. We develop a simplified RNA model for discrete molecular dynamics (DMD) simulations, incorporating base-pairing and base-stacking interactions. We demonstrate correct folding of 150 structurally diverse RNA sequences. The majority of DMD-predicted 3D structures have < 4 angstrom deviations from experimental structures. The secondary structures corresponding to the predicted 3D structures consist of 94% native base-pair interactions. Folding thermodynamics and kinetics of tRNA(Phe), pseudoknots, and mRNA fragments in DMD simulations are in agreement with previous experimental findings. Folding of RNA molecules features transient, non-native conformations, suggesting non-hierarchical RNA folding. Our method allows rapid conformational sampling of RNA folding, with computational time increasing linearly with RNA length. We envision this approach as a promising tool for RNA structural and functional analyses.