Molecular dynamics simulations of PNA•DNA and PNA•RNA duplexes in aqueous solution

Molecular dynamics simulations have been used to study the structure and flexibility of a DNA.PNA duplex and a RNA.PNA duplex in aqueous solution. In this study, trajectories have been generated starting from three different conformations of the PNA.DNA and PNA.RNA duplexes: A-like, B-like, and P-A/B-like. For the DNA PNA duplex, the three trajectories converge within the nanosecond time scale to give structures resembling closely the P-B model. The RNA PNA duplex trajectories started from A- and P-A-forms converge to give structures resembling the P-A model, but the trajectory begun from the B-like conformation leads to an unfolded duplex. Despite the similarity between P-A and P-B structures calculations show the existence of important differences in terms of molecular recognition between both conformations. Analysis of the trajectories shows that the PNA backbone is very flexible provided that the backbone movements do not alter the positioning of the bases. It is found that PNA is able to distort the structure of RNA and especially DNA strands during the formation of the PNA.DNA and PNA.RNA hybrids. The impact of these findings in antigene and antisense therapies is discussed.