Molecular dynamics simulations of cyclohexyl modified peptide nucleic acids (PNA).

Peptide Nucleic Acids (PNA) that bind sequence specifically to DNA/RNA are of major interest in the field of molecular biology and could form the basis for gene-targeted drugs. Molecular dynamics simulations are aimed to characterize the structural and dynamical features to understand the effect of backbone modification on the structure and dynamics along with the stability of the resulting 10mer complexes of PNA with DNA/RNA. Twelve Molecular Dynamics (MD) simulations of duplexes and triplexes with and without cyclohexyl modification were carried out for 10ns each. The simulations indicate that the cyclohexyl modification with different stereoisomers has influenced all the PNA-DNA/RNA complexes. Modification has added rigidity to backbone by restricting beta to +60 in case of (1R,2S) cyclohexyl PNA and to -60 in case of (1S,2R) cyclohexyl PNA. The results of MD simulations were able to show the backbone rigidification and preference for RNA complexes over DNA due to presence of cyclohexyl ring in the PNA backbone.