Center for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology, Gachibowli, Hyderabad 500032, India.
J Phys Chem B. 2010 Mar 11;114(9):3307-20. doi: 10.1021/jp910226e.
Base pairs belonging to the cis Hoogsteen:sugar-edge (H:S) family play important structural roles in folded RNA molecules. Several of these are present in internal loops, where they are involved in interactions leading to planar dinucleotide platforms which stabilize higher order structures such as base triplets and quartets. We report results of analysis of 30 representative examples spanning 16 possible base pair combinations, with several of them showing multimodality of base pairing geometry. The geometries of 23 of these base pairs were modeled directly from coordinates extracted from RNA crystal structures. The other seven were predicted structures which were modeled on the basis of observed isosteric analogues. After appropriate satisfaction of residual valencies, these structures were relaxed using the B3LYP/6-31G(d,p) method and interaction energies were derived at the RIMP2/aug-cc-pVDZ level of theory. The geometries for each of the studied base pairs have been characterized in terms of the number and nature of H-bonds, rmsd values observed on optimization, base pair geometrical parameters, and sugar pucker analysis. In addition to its evaluation, the nature of intermolecular interaction in these complexes was also analyzed using Morokuma decomposition. The gas phase interaction energies range between -5.2 and -20.6 kcal/mol and, in contrast to the H:S trans base pairs, show enhanced relative importance of the electron correlation component, indicative of the greater role of dispersion energy in stabilization of these base pairs. The rich variety of hydrogen bonding pattern, involving the flexible sugar edge, appears to hold the key to several features of structural motifs, such as planarity and propensity to participate in triplets, observed in this family of base pairs. This work explores these aspects by integrating database analysis, and detailed base pairing geometry analysis at the atomistic level, with ab initio computation of interaction energies. The study, involving alternative classification of base pairs and triplets, provides insights into intrinsic properties of these base pairs and their possible structural and functional roles.
碱基对属于顺式 Hoogsteen：糖边缘（H:S）家族，在折叠 RNA 分子中发挥着重要的结构作用。其中有几个存在于内部环中，它们参与导致平面二核苷酸平台的相互作用，这些平台稳定了更高阶的结构，如碱基三联体和四联体。我们报告了分析跨越 16 种可能碱基对组合的 30 个代表性实例的结果，其中一些显示出碱基配对几何形状的多模态性。其中 23 个碱基对的几何形状是直接从 RNA 晶体结构中提取的坐标建模的。其他七个是基于观察到的等排类似物预测的结构。在适当满足剩余价后，使用 B3LYP/6-31G(d,p)方法对这些结构进行松弛，并在 RIMP2/aug-cc-pVDZ 理论水平上得出相互作用能。对每个研究碱基对的结构进行了特征描述，包括氢键的数量和性质、优化过程中观察到的均方根偏差值、碱基对几何参数和糖构象分析。除了评估外，还使用 Morokuma 分解分析了这些复合物中分子间相互作用的性质。气相相互作用能在-5.2 到-20.6 kcal/mol 之间，与 H:S 反式碱基对相比，显示出电子相关成分的相对重要性增强，表明色散能在这些碱基对的稳定中起着更大的作用。涉及灵活糖边缘的丰富氢键模式，似乎是这些碱基对家族中结构基序的几个特征的关键，例如平面性和参与三联体的倾向。这项工作通过整合数据库分析和原子水平的详细碱基配对几何分析以及从头计算相互作用能，探索了这些方面。该研究涉及碱基对和三联体的替代分类，提供了对这些碱基对固有性质及其可能的结构和功能作用的深入了解。
