Structure and Dynamics of Phosphate Linkages and Sugars in an Abasic Hexaloop RNA Hairpin

Abstract

Hairpins containing hexaloops are well represented among the diverse conformations adopted by the RNA molecules. To investigate the intrinsic properties of a backbone submitted to a hexaloop fold, we present here a molecular dynamics study of an abasic hexaloop closed by an A-form 6 basepair stem. The analysis of the 23 ns trajectory made in explicit solvent shows that both the sugars and the torsion angles in the loop undergo numerous conformational transitions. The south sugars, although not in a majority, are the major actors of the loop stretching. The five torsion angles, ɛ, ζ, α, β, and γ, are unequally variable, and only ζ and α exhibit trimodal distributions. The analysis of the phosphate linkages in terms of ɛ- ζ ˜ - α ˜ - β ˜ - γ-combinations allows us to define five conformational families, each one composed of one major substate in equilibrium with several less populated ones. The transitions between the substates within a family follow specific pathways involving the angles ɛ, ζ, and α. Thus, this work reveals that the backbone conformational space is both reduced and ordered even in a hexaloop devoid of bases.