Unfolding mechanism and the free energy landscape of a single stranded DNA i-motif

We present Molecular Dynamics simulations of a single stranded unprotonated DNA i-motif in explicit solvent. Our results indicate that the native structure in non-acidic solution at 300 K is unstable and completely vanishes on a time scale up to 10 ns. Two unfolding mechanisms with decreasing connectivity between the initially interacting nucleobases can be identified where one pathway is characterized as entropically more favorable. The entropic preference can be mainly explained by strong water ordering effects due to hydrogen bonds for several occurring structures along the pathways. Finally we are able to indicate via free energy calculations the most stable configurations belonging to distinct hairpin structures in good agreement to experimental results.