Molecular mechanics calculations on a triple stranded DNA involving C+.G-Tand T.A(+)-C mismatched base triples

We have carried out molecular modeling of a triple stranded pyrimidine(Y) . purine(R) : pyrimidine(Y) (where ':' refers to Watson-Crick and '.' to Hoo gsteen bonding) DNA, formed by a homopurine (d-TGAGGAAAGAAGGT) and homo-pyr imidine (d-CTCCTTTCTTCC). Molecular mechanics calculations using NMR constr aints have provided a detailed three dimensional structure of the tripler. The entire stretches of purine and the pyrimidine nucleotides have a confor mation close to B-DNA. The three strands are held by the canonical C+.G:C a nd T.A:T hydrogen bonds. The structure also contains two mismatch C+.G-T an d T.A(+)-C base triples which have been characterized for the first time. I n the A(+)-C base-pair of the T.A(+)-C triple, both hydrogen donors are sit uated on the purine (A(+)(1N) and A(+)(6N)). We observe a unique hydrogen b onding interaction scheme in case of C+.G-T where one acceptor, G(6O), is b onded to three donors (C+(3NH), C+(4NH(2)) and T(3NH)). Though the C+.G-T b ase triple is less stable than C+.G:C, it is significantly more stable than T.A:T. On the other hand, T.A(+)-C is as stable as the T.A:T base triad.