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

Abstract

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.

Systematic detection of hidden complexities in the unfolding mechanism of a cytosine-rich DNA strand

“…19 that high temperature simulations at 500 K are able to reconstruct the unfolding pathway in good agreement to 300 K. Thus the main unfolding pathways can be also analyzed at higher temperatures which allows a significant decrease of simulation times to observe rare events 19 . It was also indicated that the global equi-librium structure of the hairpin configurations is shifted towards a fully unfolded strand at higher temperatures which was explained by a temperature-dependent entropy due to the interactions with the environment 18 . In this paper we want to study the transition mechanism between the hairpin configuration and a fully unfolded structure at high temperatures in detail.…”

“…It was suggested that the choice of inappropriate collective variables may also cause significant deviations in the corresponding free energy landscapes due to the presence of hysteresis effects 17 . In recent publications 18,19 we have in detail discussed the corresponding stable conformations of a deprotonated i-motif as well as the possible transition pathways. The unfolding mechanism was mainly studied in terms of a principal component analysis [18][19][20] with the corresponding eigenvectors.…”

“…In recent publications 18,19 we have in detail discussed the corresponding stable conformations of a deprotonated i-motif as well as the possible transition pathways. The unfolding mechanism was mainly studied in terms of a principal component analysis [18][19][20] with the corresponding eigenvectors. The eigenvectors are ranked due to the strength of the relative positional fluctuations of the atoms such that the lowest eigenvectors correspond to the main collective motion.…”

“…The eigenvectors are ranked due to the strength of the relative positional fluctuations of the atoms such that the lowest eigenvectors correspond to the main collective motion. It was shown that the key mechanism of unfolding can be described by the first two eigenvectors of the system where most of the important motion is involved 18,19 . We have shown 18,19 that an unfolding mechanism between hairpin configurations and a fully unfolded structure is mainly oppressed due to energetic barriers and deep free energy minima.…”

“…It was shown that the key mechanism of unfolding can be described by the first two eigenvectors of the system where most of the important motion is involved 18,19 . We have shown 18,19 that an unfolding mechanism between hairpin configurations and a fully unfolded structure is mainly oppressed due to energetic barriers and deep free energy minima. Additionally it was reported in Ref.…”