Unraveling the structural complexity in a single-stranded RNA tail: implications for efficient ligand binding in the prequeuosine riboswitch

Eichhorn, Catherine D.; Feng, Jun; Suddala, Krishna C.; Walter, Nils G.; Brooks, Charles L.; Al-Hashimi, Hashim M.

Much of our understanding of the conformational behavior of ssRNA comes from high-resolution NMR and X-ray structures of RNA, in which ssRNA directly engages in tertiary or RNA-protein interactions. However, the atomic-level structural and dynamic behavior of these elements in the absence of these interactions remains unclear, in large part due to their high degree of flexibility. Several studies suggest that ssRNA polynucleotides adopt stacked and partially helical conformations, particularly adenine-rich sequences; however, the biological relevance of these structures is unclear (11) (12) (13) (14) (15) (16) (17) . Atomic-resolution studies of ssRNA are scarce: at present only one isosequential ssRNA and ssDNA sequence has been characterized by homonuclear NMR methods and shown to possess properties reminiscent of A-form and B-form helices, respectively (18) . Few MD studies have been performed on ssRNA, the majority of which use the AMBER force field (19, 20) to explore the impact of chemical modifications such as peptide nucleic acids (PNA) and O2 0 -methylation (21) (22) (23) (24) .