Noncanonical hydrogen bonding in nucleic acids. Benchmark evaluation of key base-phosphate interactions in folded RNA molecules using quantum-chemical calculations and molecular dynamics simulations.
Noncanonical hydrogen bonding in nucleic acids. Benchmark evaluation of key base-phosphate interactions in folded RNA molecules using quantum-chemical calculations and molecular dynamics simulations.
复制标题
DOI：
10.1021/jp204820b
复制
发表时间：
2011-09
期刊：
影响因子：
--
通讯作者：
Marie Zgarbová;P. Jurečka;P. Banáš;M. Otyepka;J. Šponer;N. Leontis;Craig L. Zirbel;Jiřı́ Šponer
中科院分区：
文献类型：
--
作者：
Marie Zgarbová;P. Jurečka;P. Banáš;M. Otyepka;J. Šponer;N. Leontis;Craig L. Zirbel;Jiřı́ Šponer
RNA分子是稳定的广泛的非规范相互作用，不存在于DNA。其中，最近分类的碱-磷酸盐（BPh）相互作用是最重要的相互作用。核糖体晶体结构中12%的核苷酸参与BPh的相互作用。BPh相互作用是高度保守的，是RNA序列进化的主要制约因素。在这里，我们使用MP2计算来评估BPh相互作用的能量学，这些计算外推到原子轨道的完整基集，并对高阶电子相关效应进行了修正。将参考计算与DFT-D和DFT-D3方法、SAPT方法和分子力学力场进行了比较。计算除了提供BPh相互作用的基本基准外，还允许对原始分类进行一些改进，包括识别一些潜在的双键BPh模式。参考计算之后，分析了一些较大的RNA片段，考虑了BPh相互作用的背景。计算证明了利用BPh相互作用在真实RNA结构中的相互作用模式的复杂性。BPh相互作用通常涉及复杂的相互作用网络。我们研究了质子化腺嘌呤与发簪核酶的相互作用，发簪核酶是肌毒素-蓖麻毒素环S-turn基序中关键的BPh相互作用，这可能预先决定了glmS核开关的S-turn拓扑结构和复杂的BPh模式。最后，在显式溶剂分子动力学模拟中评估了BPh相互作用的结构稳定性。模拟很好地保留了关键的BPh相互作用，并允许解剖结构/功能重要的水介导BPh桥，这在早期的BPh相互作用生物信息学分类中无法考虑。
RNA molecules are stabilized by a wide range of noncanonical interactions that are not present in DNA. Among them, the recently classified base-phosphate (BPh) interactions belong to the most important ones. Twelve percent of nucleotides in the ribosomal crystal structures are involved in BPh interactions. BPh interactions are highly conserved and provide major constraints on RNA sequence evolution. Here we provide assessment of the energetics of BPh interactions using MP2 computations extrapolated to the complete basis set of atomic orbitals and corrected for higher-order electron correlation effects. The reference computations are compared with DFT-D and DFT-D3 approaches, the SAPT method, and the molecular mechanics force field. The computations, besides providing the basic benchmark for the BPh interactions, allow some refinements of the original classification, including identification of some potential doubly bonded BPh patterns. The reference computations are followed by analysis of some larger RNA fragments that consider the context of the BPh interactions. The computations demonstrate the complexity of interaction patterns utilizing the BPh interactions in real RNA structures. The BPh interactions are often involved in intricate interaction networks. We studied BPh interactions of protonated adenine that can contribute to catalysis of hairpin ribozyme, the key BPh interaction in the S-turn motif of the sarcin-ricin loop, which may predetermine the S-turn topology and complex BPh patterns from the glmS riboswitch. Finally, the structural stability of BPh interactions in explicit solvent molecular dynamics simulations is assessed. The simulations well preserve key BPh interactions and allow dissection of structurally/functionally important water-meditated BPh bridges, which could not be considered in earlier bioinformatics classification of BPh interactions.