Determination of a set of parameters for the molecular modelling of phosphorothioate DNA

Phosphorothioate DNAs, have emerged as a new class of potent drugs. They are obtained by the replacement of the anionic oxygens of the phophodiester backbone by sulphur. A set of parameters has been developed for the FLEX force field implemented in JUMNA 10.0 to take into account the influence of sulphur on the structure of the DNA double helix. The consistency of our parameters was tested by modelling a phosphorothioate oligomer namely d(GC)8. d(GC)8. Results, obtained on both R-ps and S-ps diastereoisomers, were compared to the phosphodiester counterpart and are in agreement with available experimental data. Thus, our set of parameters seems suitable for further molecular modelling of other phosphorothioate oligomers.