Molecular Mechanics Calculations on a Triple Stranded DNA Involving C⁺.G-T and T.A⁺-C Mismatched Base Triples

Abstract

We have carried out molecular modeling of a triple stranded pyrimidine(Y). purine (R): pyrimidine(Y) (where ‘:’ refers to Watson-Crick and ‘.’ to Hoogsteen bonding) DNA, formed by a homo- purine (d-TGAGGAAAGAAGGT) and homo-pyrimidine (d-CTCCTTTCTTCC). Molecular mechanics calculations using NMR constraints have provided a detailed three dimensional structure of the triplex. The entire stretches of purine and the pyrimidine nucleotides have a conformation close to B-DNA. The three strands are held by the canonical C⁺.G:C and T.A:T hydrogen bonds. The structure also contains two mismatch C⁺.G-T and T.A⁺-C base triples which have been characterized for the first time. In the A⁺-C base-pair of the T.A⁺-C triple, both hydrogen donors are situated on the purine (A⁺(1N) and A⁺(6N)). We observe a unique hydrogen bonding interaction scheme in case of C⁺.G-T where one acceptor, G(60), is bonded to three donors (C⁺(3NH), C⁺(4NH₂) and T(3NH)). Though the C⁺.G-T base 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.