Molecular dynamics of duplex systems involving PNA: Structural and dynamical consequences of the nucleic acid backbone

Molecular modeling and molecular dynamics simulation studies have been performed on homo-and heteroduplexes involving peptide nucleic acids (PNA) in aqueous solution under periodic boundary conditions. PNA is a DNA analogue that is homomorphous to DNA, but has an electrically neutral pseudopeptide backbone. In the present study we have investigated the structure and dynamics of duplex systems involving PNA in aqueous solution and how the overall structural and dynamical features of a double helix depend on the nature of the backbones of the constituent strands. Four different duplex systems have been studied: (i) PNA-PNA duplex (1.15 ns), (ii) PNA-DNA antiparallel duplex (0.64 ns), (iii) PNA-DNA parallel duplex (0.6 ns), and (iv) DNA-DNA duplex (0.64 ns). Comparison of the structural features obtained from this study on PNA-DNA antiparallel and PNA-PNA duplex systems with those obtained from NMR and X-ray crystallographic studies respectively has shown very good agreement. In all the cases the structures were stable over the entire period of simulations and the results indicate that the complementary bases and a backbone homomorphous to DNA are sufficient to maintain a stable double helix. The antiparallel PNA-DNA duplex and the PNA-PNA duplex have average structures between A-and B-helixes with certain A-like features while the parallel PNA-DNA double helix, as predicted in this study, is more close to the B-helix. No major difference in the geometries and dynamics of the base pairs in the different duplexes was found. However, the helicoidal parameters are found to be different for the different duplexes. These indicate that the actual structure is determined by the base pairing and the base stacking with the backbones causing some perturbations to this basic structure. The internal dynamics in the base linker region shows highly restricted motions even in the PNA strands where there is no ribose ring.