Structural diversity and isomorphism of hydrogen-bonded base interactions in nucleic acids.

The wide structural diversity of RNA results in part from the diversity of non-Watson-Crick interactions between bases. To examine the repertoire of possible hydrogen bond interactions among bases, we computed databases of base-pairs and base-triples by systematically matching all possible hydrogen-bond donors and acceptors between bases and evaluating the geometries of each planar configuration. For base-pairs, we find 53 arrangements having at least two hydrogen bonds, including 23 pairs with protonated bases that have not previously been modeled. A comparison with experimentally observed base-pairs reveals an unexpected G:U pair recently observed in the ribosome. For base-triples, we find 840 arrangements in which the three bases are constrained by a total of at least three hydrogen bonds. Base-triples in particular exhibit a wide range of structural diversity, suggesting how compact or elongated nucleic acid structures may be constructed using different hydrogen-bonding patterns. Base-pair and base-triple conformations were systematically compared to identify structurally isomorphic combinations, and the experimentally observed arrangements within double and triple helices are among the most isomorphic. Unexpectedly, however, other combinations in the database are even more isomorphic, including several in which all-purine arrangements overlap with all-pyrimidine arrangements. These studies highlight some of the combinatoric and geometric versatility of base interactions and help provide a framework for analyzing and modeling isomorphic interactions and potentially for designing novel nucleic acid structures.