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

Abstract

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 ®eld implemented in JUMNA 10.0 to take into account the in¯uence 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-p S and S-p S 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.

Advances in biomolecular simulations: methodology and recent applications

“…Force-field parameters for phosphorothioate DNA have been determined (Bertrand et al 1999). These parameters took into account the sulfur effect on structure and were incorporated into the FLEX force field in JUMNA (Lavery et al 1995).…”

DFT Study of the Silyl Esters of Thiophosphorus Acids

“…Theoretical studies of small phosphate and thiophosphate models is an important step toward a detailed understanding of many biochemical processes at the atomic level [22][23][24][25][26]. We present here theoretical predictions of some structural features and reactivity aspects, in particular, thiono-thiolo isomerization of model silyl esters of oxyand thio-phosphorus acids, that have never received even a cursory theoretical explication.…”