Abstract

Abstract. The base pairing patterns in RNA structures are more versatile and completely different as compared to DNA. We present here results of ab-initio studies of structures and interaction energies of eight selected RNA base pairs reported in literature. Interaction energies, including BSSE correction, of hydrogen added crystal geometries of base pairs have been calculated at the HF/6-31G** level. The structures and interaction energies of the base pairs in the crystal geometry are compared with those obtained after optimization of the base pairs. We find that the base pairs become more planar on full optimization. No change in the hydrogen bonding pattern is seen. The dipole moments of the bases are reduced on full optimization. It is expected that the inclusion of appropriate considerations of many of these aspects of RNA base pairing would significantly improve the accuracy of RNA secondary structure prediction.

Abstract

Abstract The trans Watson-Crick/Watson-Crick family of base pairs represent a geometric class which 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 which enable sequentially distant regions to interact with each other in. 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 Molecule 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 for non protonated base pairs 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 . 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 functional geometry of base pairs and the nature of their local interaction energy hyperspace, in conjunction with tertiary and neighboring group interaction potentials in the global context, could be correlated with the identities of free and bound hydrogen bond donor/acceptor groups present in interacting bases. It also suggests that the concept of isostericity alone may not always determine covariation potentials for base pairs, particularly those which may be participating in functional 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.