A theoretical study of the interaction of monomethylammonium with double‐stranded oligonucleotides

Theoretical computations are performed of the interaction specificities of the monomethylammoniumion with double‐stranded oligonucleotides (dPu) n ·(dPy) n in the B‐DNA conformation. The effects of base sequence and chain length are examined. In short oligomers ( n = 2, 3), the interaction energies of the cation are larger in the major groove of (dG) n ·(dC) n than in the minor groove of (dA) n ·(dT) n . As a consequence of further shaping of the grooves and building up of the phosphates, a marked reversal in the affinities of the cation for the grooves occurs at the (dPu) 5 ·(dPy) 5 and the p(dPu) 5 p·p(dPy) 5 p levels: it is the binding in the minor groove of the adenine‐thymine oligomers that provides then the most favorable interaction energies. It is also shown, at the level of the double helices built from dinucleoside monophosphates, that the interaction of monomethylammonium in the minor groove occurs in specific configurations involving the three NH bonds of the cation, and two successive bases on one strand; this binding is sequence‐specific, the order of inherent preferences being (TpA) > (TpT) > (ApA) > (ApT).