Theoretical study of the guanine –> 6-thioguanine substitution in duplexes, triplexes, and tetraplexes.

Molecular dynamics and thermodynamic integration calculations have been carried out on a set of G-rich single-strand, duplex, triplex, and quadruplex DNAs to study the structural and stability changes connected with the guanine –> 6-thioguanine (G –> S) mutation. The presence of 6-thioguanine leads to a shift of the geometry from the B/A intermediate to the pure B-form in duplex DNA. The G –> S mutation does not largely affect the structure of the antiparallel triplex when it is located at the reverse-Hoogsteen position, but leads to a non-negligible local distortion in the structure when it is located at the Watson-Crick position. The G –> S mutation leads to destabilization of all studied structures: the lowest effect has been observed for the G –> S mutation in the reverse-Hoogsteen strand of the triplex, a medium effect has been observed in the Watson-Crick strand of the triplex and duplex, and the highest influence of the G –>S mutation has been found for the quadruplex structures.