A MOLECULAR-DYNAMICS COMPUTER-SIMULATION STUDY OF NUCLEOTIDE ANALOGS - 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 analo gue 2, have been studied using Molecular Dynamics (MD) computer simula tion. It was found that the methylphosphonate modification leads to si gnificant changes in the coordination of water molecules around the in ternucleotidic linkage and these, in turn, affect the hydration patter n of other parts of the molecule. The most notable differences between Rp and Sp diastereomers 2a and 2b were found to occur at the deoxyrib ose moieties of the nucleosid-5'-yl units.