A molecular dynamics computer simulation study of nucleotide analogues. Comparison of the hydration pattern of dithymidine phosphate with those of the dithymidine methylphosphonate diastereomers

The hydration pattern of thymidyl(3' --> 5') thymidine 1 and those of R-p and S-p diastereomers of the corresponding methylphosphonate analogue 2, have been studied using Molecular Dynamics (MD) computer simulation. It was found that the methylphosphonate modification leads to significant changes in the coordination of water molecules around the internucleotidic linkage and these, in turn, affect the hydration pattern of other parts of the molecule. The most notable differences between Rp and Sp diastereomers 2a and 2b were found to occur at the deoxyribose moieties of the nucleosid-5'-yl units.