Deprotonation mechanism of a single-stranded DNA i-motif†
We present the detailed deprotonation mechanism of a fully protonated DNA i-motif as studied by all-atom Molecular Dynamics simulations. The associated unfolding of the i-motif is driven by the application of the Metadynamics method. The release of two protons, which stabilize the hemi-protonated cytosine pairs in the native i-motif, can be identified as the initial step for the occurrence of the unfolding process. By a systematic analysis of the proton motion, we are able to validate a two-step deprotonation mechanism. Our findings are in excellent agreement to experimental results that have been recently published.