Sponer Judit E, Spackova Nad'a, Leszczynski Jerzy, Sponer Jirí
Institute of Biophysics, Academy of Sciences of the Czech Republic, Kralovopolska 135, 612 65 Brno, Czech Republic.
J Phys Chem B. 2005 Jun 9;109(22):11399-410. doi: 10.1021/jp051126r.
Due to the presence of the 2'-OH hydroxyl group of ribose, RNA molecules utilize an astonishing variability of base pairing patterns to build up their structures and perform the biological functions. Many of the key RNA base pairing families have no counterparts in DNA. In this study, the trans Watson-Crick/sugar edge (trans WC/SE) RNA base pair family has been characterized using quantum chemical and molecular mechanics calculations. Gas-phase optimized geometries from density functional theory (DFT) calculations and RIMP2 interaction energies are reported for the 10 crystallographically identified trans WC/SE base pairing patterns. Further, stable structures are predicted for all of the remaining six possible members of this family not seen in RNAs so far. Among these novel six base pairs, the computations substantially refine two structures suggested earlier based on simple isosteric considerations. For two additional trans WC/SE base pairs predicted in this study, no arrangement was suggested before. Thus, our study brings a complete set of trans WC/SE base pairing patterns. The present results are also contrasted with calculations reported recently for the cis WC/SE base pair family. The computed base pair sizes are in sound correlation with the X-ray data for all WC/SE pairing patterns including both their cis and trans isomers. This confirms that the isostericity of RNA base pairs, which is one of the key factors determining the RNA sequence conservation patterns, originates in the properties of the isolated base pairs. In contrast to the cis structures, however, the isosteric subgroups of the trans WC/SE family differ not only in their H-bonding patterns and steric dimensions but also in the intrinsic strength of the intermolecular interactions. The distribution of the total interaction energy over the sugar-base and base-base contributions is controlled by the cis-trans isomerism.
由于核糖具有2'-OH羟基，RNA分子利用碱基配对模式的惊人变异性来构建其结构并执行生物学功能。许多关键的RNA碱基配对家族在DNA中没有对应物。在本研究中，通过量子化学和分子力学计算对反式沃森-克里克/糖边缘（trans WC/SE）RNA碱基配对家族进行了表征。报告了密度泛函理论（DFT）计算得到的气相优化几何结构以及10种晶体学鉴定的反式WC/SE碱基配对模式的RIMP2相互作用能。此外，还预测了该家族目前在RNA中尚未发现的其余六个可能成员的稳定结构。在这六个新的碱基对中，计算结果显著优化了之前基于简单等排体考虑提出的两种结构。对于本研究中预测的另外两个反式WC/SE碱基对，之前没有提出过任何排列方式。因此，我们的研究给出了一套完整的反式WC/SE碱基配对模式。目前的结果也与最近报道的顺式WC/SE碱基配对家族的计算结果进行了对比。计算得到的碱基对大小与所有WC/SE配对模式（包括其顺式和反式异构体）的X射线数据具有良好的相关性。这证实了RNA碱基对的等排性是决定RNA序列保守模式的关键因素之一，其源于孤立碱基对的性质。然而，与顺式结构不同，反式WC/SE家族的等排亚组不仅在氢键模式和空间尺寸上不同，而且在分子间相互作用的内在强度上也不同。总相互作用能在糖-碱基和碱基-碱基贡献上的分布受顺反异构现象控制。
