Fully solvated molecular dynamics simulations of duplexes formed by modified oligonucleotides with xylo/phosphodiesteric and xylo/phosphonate internucleoside linkages and their natural counterpart Original Research Article

The impact of the xylo/phosphodiesteric and xylo/phosphonate internucleoside linkage modification on the ability of the modified oligonucleotide to hybridize with a natural DNA strand was studied by fully solvated molecular dynamics (MD) simulations. Three undecamer complexes were analyzed: natural dT11.dA11 duplex as a reference and two of its analogs with modified linkages in the deoxyadenosine chain. The modified linkages were of the 5′OPO2O3′XYLO (AX) or 5′OPO2CH2O3′XYLO (ACX) type. Simulations were performed by using the AMBER 5.0 software package with the force field completed by a set of parameters needed to model the modified segments of the ACX oligonucleotide. Both modifications were found to lead to stable double helical complexes at 300 K.