Triple helical DNA in a duplex context and base pair opening

It is fundamental to explore in atomic detail the be-havior of DNA triple helices as a means to understand the role they might play in vivo and to better engi-neer their use in genetic technologies, such as anti-gene therapy. To this aim we have performed atom-istic simulations of a purine-rich antiparallel triple helix stretch of 10 base triplets flanked by canoni-cal Watson–Crick double helices. At the same time we have explored the thermodynamic behavior of a flipping Watson–Crick base pair in the context of the triple and double helix. The third strand can be ac-commodated in a B-like duplex conformation. Upon binding, the double helix changes shape, and be-comes more rigid. The triple-helical region increases its major groove width mainly by oversliding in the negative direction. The resulting conformations are somewhere between the A and B conformations with base pairs remaining almost perpendicular to the he-lical axis. The neighboring duplex regions maintain a B DNA conformation. Base pair opening in the du-plex regions is more probable than in the triplex and binding of the Hoogsteen strand does not influence base pair breathing in the neighboring duplex region