Folding of nucleic acids.

Abstract

This paper describes and discusses nucleic acid conformations, the energy contributions that stabilize them, and the ways the stable conformations are formed. Preferred conformations of nucleotides and of double, triple and super helices in nucleic acids are described briefly. Next the enthalpy and entropy of nucleic acid order/disorder transitions are reviewed. It is concluded that (a) the double helix is stabilized primarily by interbase hydrogen bonds, and (h) the available thermodynamic parameters for single-strand stacking are probably incorrect. The conformation of single strands in solution is discussed briefly. The kinetics of helix formation is described; the transition state of three base pairs that has been proposed supports the idea that the strength of hydrogen bonds depends on the access of water molecules to the base pair. Hairpin formation and more complex secondary structures of nucleic acids are described and explained in terms of rate of formation, stability, and control of secondary structure. Transfer RNA has tertiary structure as well as secondary structure. Schematic diagrams are used to show how experimental evidence fixes different parts of the tRNA tertiary structure. The detailed interactions in the proposed model are supported by the sequence of cell-wall glycine tRNA, which can be charged with an amino acid without participating in protein synthesis. Sequential steps in the folding and unfolding of the proposed tRNA conformation are outlined. Finally, the abilities of nucleic acids and proteins to form stable tertiary structures are compared and the evolutionary consequences are considered. Nucleic acids and proteins have been studied intensively over the past 25 years. Although similar techniques have been used on each of these important classes of macromolecule, available information for each is very different. X-ray diffraction methods have elucidated conformations of both nucleic acids and proteins but, whereas the known conformations of different proteins are very different, those of nucleic acids are all simple variants of the Watson-Crick double helix. It is easier, however, to study nucleic acid conformations in