THEORETICAL-STUDIES OF DNA-RNA HYBRID CONFORMATIONS

Molecular modelling has been used to probe the conformational preferences of double stranded DNA - RNA hybrids. As might be expected, the sugars of the DNA strand have higher conformational flexibility, but, for the majority of the repetitive sequences studied, these sugars prefer a C-2'-endo pucker, while ribose sugars uniformly adopt a C-3'-endo pucker. This gives rise to a strongly heteronomous duplex conformation. One exception to this rule involves the thymidine strand of poly(dT).poly(rA), which marginally prefers a C-3'-endo pucker. Our study further indicates that the DNA strands of the hybrids favour backbone torsions in the canonical B domain, rather than the modified values proposed on the basis of fibre diffraction studies. Backbone conformational transitions can nevertheless be induced leading to an alpha gamma-flip (alpha:gamma, g(-)/g(+) -> t/t) or to the alpha beta gamma-flip form proposed from fibre studies (alpha:beta:gamma, g(-)/t/g(+) -> t/g(+)/t). The latter transition is also found to be linked to B-I -> B-II transitions (epsilon:xi, t/g(-) -> g(-)/t).