Molecular Dynamics of Double Stranded Xylo-Nucleic Acid

Xylo-nucleic acid (XyloNA) is a synthetic analogue of ribo-nucleic acid (RNA), where the ribose sugar has been replaced by xylose. We present a molecular dynamics study of the conformational evolution of XyloNA double strand oligomers derived from A-RNA through the substitution of β-d-ribofuranose by β-d-xylofuranose and having lengths of 8, 16, and 29 base pairs, using a set of independent all-atom simulations performed at various time scales ranging from 55 to 100 ns, with one long 500 ns simulation of the 29-mer. In order to validate the robustness of XyloNA conformation, a set of simulations using various cutoff distances and solvation box dimensions has also been performed. These independent simulations reveal the uncoiling or elongation of the initial conformation to form an open ladder type transient state conformation and the subsequent formation of a highly flexible duplex with a tendency to coil in a left-handed fashion. The observed open ladder conformation is in line with recently obtained NMR data on the XyloNA 8-mer derived using 5'-d(GUGUACAC)-3'. The observed negative interbase pair twist leads to the observed highly flexible left-handed duplex, which is significantly less rigid than the stable left-handed dXyloNA duplex having a strong negative twist. A comparison between the xylo-analogues of DNA and RNA shows a clear distinction between the helical parameters, with implications for the pairing mechanism.