A 1.5 ns long molecular dynamics simulation was conducted to compare the structure and stability of a model DNA triplex in saline solution with that found from experiments. The model DNA was an antiparallel py-pu-pu (CG-G) 7-mer structure which contained a GC-T mismatch triplet at the middle of the sequence. The local conformation of the mismatch triplet and the effects of this triplet on the global helical structure suggest that the GC-T triplet forms stable hydrogen bonds and shows distortions from an in-plane alignment. The overall rms deviation of the triplex is similar to one without a mismatch, although the thymine base in the mismatch triplet shows significantly higher mobility. A high coordination probability for water between the G and T bases in the mismatch triplet was observed to have an effect on the stability of non-hydrogen-bonded base pairs. Average helical parameters, sugar pucker, and backbone dihedral angles indicate that the CG-G triplets on the 3’ side of the mismatch triplet possess different structural and dynamical properties than that of the 5’ side. These observations are consistent with recently available experimental results and provide an interpretation of the observed experimental structure. They also suggest that inclusion of explicit water molecules is necessary in order to understand and predict the interaction between the third strand and duplex DNA.
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