MOLECULAR-DYNAMICS SIMULATION OF THE DNA TRIPLEX D(TC)5.D(GA)5.D(C+T)5

A molecular dynamics simulation of the DNA triple helix d(TC)5 · d(GA)5 · d(C+T)5 is described (C+ represents a protonated cytosine residue). The simulation has been performed using the program AMBER 3·1 and includes counterions and explicit solvent under periodic boundary conditions. Both the dynamic and time-averaged behaviour of the system has been analysed. Considerable deviations from the fibre-diffraction model for DNA triple helix structure are observed, including the repuckering of the purine strand sugars that has been identified in some nuclear magnetic resonance (n.m.r.) studies. The simulation suggests that this conformational change may be driven by the possibility of improved interactions between the phosphate groups of this strand and both the solvent and counterions. Several examples of a particular conformational transition are observed, involving correlated changes in the backbone angles alpha and gamma. These transitions provide a possible explanation for some unusual n.m.r. data that have been reported. The structure of the triple helix major groove also suggests an explanation for the observed stabilization of DNA triplexes by polyvalent cations, and their ability to interact with drugs that bind in the minor groove of DNA duplexes. © 1992.