Molecular modelling of the 3-D structure of RNA tetraloops with different nucleotide sequences.

One surprisingly common element of RNA secondary structure consists of a hairpin capped by a four-base loop (or the tetraloop). Recently the 3-D structures of two RNA-tetraloops have been determined by NMR-studies. Both structures have a similar architecture: the first and the last bases of the loop form a hydrogen bonded pair which is stacked on the stem base pair. We have analysed the ability of tetraloops, with the other combinations of the first and the fourth bases, to adopt such a 'diloop' conformation using computer modelling. The analysis has shown that the 'diloop' conformation has many covalent and steric constraints which give a possibility for reliable structural predictions. As a result, a set of the tetraloop 3-D structures in which hydrogen bonded pairing of the first and the last bases does not cause covalent and steric hindrances has been selected. In most cases several predicted 3-D structures corresponded to one tetraloop sequence. Taking into consideration the folding pathway of RNA hairpins we have resolved this ambiguity and predicted the most probable 3-D structure for every possible nucleotide sequence of the tetraloop. On the basis of these results a conclusion has been drawn on the possible reasons of the tetraloop phylogenetic preference.