Sharma Purshotam, Mitra Abhijit, Sharma Sitansh, Singh Harjinder, Bhattacharyya Dhananjay
Center for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology, Gachibowli, Hyderabad, India.
J Biomol Struct Dyn. 2008 Jun;25(6):709-32. doi: 10.1080/07391102.2008.10507216.
The trans Watson-Crick/Watson-Crick family of base pairs represent a geometric class that play important structural and possible functional roles in the ribosome, tRNA, and other functional RNA molecules. They nucleate base triplets and quartets, participate as loop closing terminal base pairs in hair pin motifs and are also responsible for several tertiary interactions that enable sequentially distant regions to interact with each other in RNA molecules. Eleven representative examples spanning nine systems belonging to this geometric family of RNA base pairs, having widely different occurrence statistics in the PDB database, were studied at the HF/6-31G (d, p) level using Morokuma decomposition, Atoms in Molecules as well as Natural Bond Orbital methods in the optimized gas phase geometries and in their crystal structure geometries, respectively. The BSSE and deformation energy corrected interaction energy values for the optimized geometries are compared with the corresponding values in the crystal geometries of the base pairs. For non protonated base pairs in their optimized geometry, these values ranged from -8.19 kcal/mol to -21.84 kcal/mol and compared favorably with those of canonical base pairs. The interaction energies of these base pairs, in their respective crystal geometries, were, however, lesser to varying extents and in one case, that of A:A W:W trans, it was actually found to be positive. The variation in RMSD between the two geometries was also large and ranged from 0.32-2.19 A. Our analysis shows that the hydrogen bonding characteristics and interaction energies obtained, correlated with the nature and type of hydrogen bonds between base pairs; but the occurrence frequencies, interaction energies, and geometric variabilities were conspicuous by the absence of any apparent correlation. Instead, the nature of local interaction energy hyperspace of different base pairs as inferred from the degree of their respective geometric variability could be correlated with the identities of free and bound hydrogen bond donor/acceptor groups present in interacting bases in conjunction with their tertiary and neighboring group interaction potentials in the global context. It also suggests that the concept of isostericity alone may not always determine covariation potentials for base pairs, particularly for those which may be important for RNA dynamics. These considerations are more important than the absolute values of the interaction energies in their respective optimized geometries in rationalizing their occurrences in functional RNAs. They highlight the importance of revising some of the existing DNA based structure analysis approaches and may have significant implications for RNA structure and dynamics, especially in the context of structure prediction algorithms.
反式沃森-克里克/沃森-克里克碱基对家族代表了一类几何结构，它们在核糖体、转运RNA（tRNA）和其他功能性RNA分子中发挥着重要的结构作用，可能还具有功能作用。它们形成碱基三联体和四联体的核心，作为发夹基序中的环封闭末端碱基对参与其中，还负责一些三级相互作用，使RNA分子中相隔较远的区域能够相互作用。在HF/6-31G(d,p)水平上，分别使用森胁分解法、分子中的原子法以及自然键轨道法，对属于该RNA碱基对几何家族的九个系统中的十一个代表性实例进行了研究，这些实例在蛋白质数据银行（PDB）数据库中的出现统计差异很大，研究分别在优化的气相几何结构及其晶体结构几何结构中进行。将优化几何结构的基组重叠误差（BSSE）和变形能校正后的相互作用能值与碱基对晶体几何结构中的相应值进行比较。对于处于优化几何结构的非质子化碱基对，这些值范围从-8.19千卡/摩尔到-21.84千卡/摩尔，与标准碱基对的值相比具有优势。然而，这些碱基对在各自晶体几何结构中的相互作用能在不同程度上较小，在一种情况下，即A:A W:W反式碱基对，实际上发现其相互作用能为正值。两种几何结构之间的均方根偏差（RMSD）变化也很大，范围从0.32 - 2.19埃。我们的分析表明，所获得的氢键特征和相互作用能与碱基对之间氢键的性质和类型相关；但出现频率、相互作用能和几何变异性明显缺乏任何明显的相关性。相反，从各自几何变异性程度推断出的不同碱基对的局部相互作用能超空间的性质，可能与相互作用碱基中存在的游离和结合氢键供体/受体基团的身份及其在整体背景下的三级和相邻基团相互作用势相关。这也表明，仅等排性概念可能并不总是决定碱基对的共变势，特别是对于那些可能对RNA动力学很重要的碱基对。在解释它们在功能性RNA中的出现情况时，这些考虑因素比它们在各自优化几何结构中的相互作用能绝对值更重要。它们突出了修订一些现有的基于DNA的结构分析方法的重要性，并且可能对RNA结构和动力学有重大影响，特别是在结构预测算法的背景下。
