STRUCTURE OF (RGGC(GA)UNDER-BARGCC)2 IN SOLUTION FROM NMR AND RESTRAINED MOLECULAR-DYNAMICS

The duplex (rGGCGAGCC)2 contains tandem G.A mismatches-a common motif in the secondary structures of biological RNAs. The three-dimensional structure of (rGGCGAGCC)2 was derived using molecular dynamics and ene rgy minimization with NMR-derived restraints for 78 interproton distan ces (per strand), 18 hydrogen bonds for the six Watson-Crick G.C pairs , and 26 dihedral angles (per strand). The G.A mismatch structures are similar to those observed in a DNA duplex [Li, Y., Zon, G., & Wilson, W. D. (1991) Proc. Natl. Acad. Sci. U.S.A. 80, 26-30] and an RNA hair pin [Heus, H. A., & Pardi, A. (1991) Science 253, 191-193], with hydro gen bonds from guanine 2-amino and N3 to adenine N7 and 6-amino, respe ctively. The other G 2-amino and A 6-amino protons are within hydrogen -bonding distance of a phosphate oxygen and 2'-oxygen, respectively. S trong interstrand A-A and G-G stacking is observed between the G.A mis matches. This contrasts with the poor stacking observed between the G. A mismatches and closing G.C base pairs. The stems are basically A-for m with all bases in the anti conformation and all nonterminal sugars i n the C3'-endo conformation. The structure rationalizes previous therm odynamic, circular dichroism, and imino proton NMR results and suggest s tandem G.A mismatches in RNA may provide a contact site for tertiary interactions.