Can oligonucleoside methylphosphonates form a stable triplet with a double DNA helix?

Molecular dynamics simulations of oligonucleoside methylphosphonates (MP) and naturally occurring oligodeoxynucleotides (ODN) as the third strand to double-stranded (ds) DNA targets predict that the third strand with MP backbone is more favorable to triple helix formation than the native phosphodiester ODN third strand. In contrast to experimental data, the calculated DNA conformations in both fully solvated triple helical system are found to be in hybrid A and B conformations. The calculations predict that a third strand with MP backbone is readily accommodated in the major groove of the ds DNA target, and adopts a different conformation from a helical triplet formed with native ODN as the third strand through the Hoogsteen base pairing scheme.