The role of backbone oxygen atoms in the organization of nucleic acid tertiary structure: zippers, networks, clamps, and C-H center dot center dot center dot O hydrogen bonds

Tight packing between structural elements is a prerequisite for molecular recognition and catalysis. In proteins, alpha-helices and beta-sheets present the amino acid side chains on the surface while the polar amide bonds are buried. The opposite is found in double-and polystranded nucleic acids, where negatively charged phosphates occupy the surface and the side chains are hydrogen bonded in the core. Thus the question arises: How do densely packed nucleic acid molecules achieve close approach, despite the repulsion between phosphates that would appear to preclude tight contacts? One obvious answer is by mediating interstrand contacts through coordinated cations that can screen the negative charges. In this contribution, however, we highlight a variety of alternative direct interactions involving atoms of the sugar-phosphate backbone that can promote tight packing of RNA and DNA into functional molecules. We have analyzed the existing nucleic acid crystal structures in terms of the presence of close contacts between backbone regions. In RNA, ribose 2'-hydroxyl groups were observed to mediate such contacts in the majority of cases. However, their absence in DNA does not prevent oligodeoxynucleotides from packing tightly, aided by various interactions between backbone atoms.