Geometric nomenclature and classification of RNA base pairs

Non-Watson-Crick base pairs mediate specific interactions responsible for R NA-RNA self-assembly and RNA-protein recognition. An unambiguous and descri ptive nomenclature with well-defined and nonoverlapping parameters is neede d to communicate concisely structural information about RNA base pairs. The definitions should reflect underlying molecular structures and interaction s and, thus, facilitate automated annotation, classification, and compariso n of new RNA structures. We propose a classification based on the observati on that the planar edge-to-edge, hydrogen-bonding interactions between RNA bases involve one of three distinct edges: the Watson-Crick edge, the Hoogs teen edge, and the Sugar edge (which includes the 2'-OH and which has also been referred to as the Shallow-groove edge). Bases can interact in either of two orientations with respect to the glycosidic bonds, cis or trans rela tive to the hydrogen bonds. This gives rise to 12 basic geometric types wit h at least two H bonds connecting the bases, For each geometric type, the r elative orientations of the strands can be easily deduced. High-resolution examples of 11 of the 12 geometries are presently available. Bifurcated pai rs, in which a single exocyclic carbonyl or amino group of one base directl y contacts the edge of a second base, and water-inserted pairs, in which si ngle functional groups on each base interact directly, are intermediate bet ween two of the standard geometries. The nomenclature facilitates the recog nition of isosteric relationships among base pairs within each geometry, an d thus facilitates the recognition of recurrent three-dimensional motifs fr om comparison of homologous sequences, Graphical conventions are proposed f or displaying non-Watson-Crick interactions on a secondary structure diagra m, The utility of the classification in homology modeling of RNA tertiary m otifs is illustrated.