posted on 2017-04-02, 00:00authored byFederico Iacovelli, Andrea Idili, Alessandro Benincasa, Davide Mariottini, Alessio Ottaviani, Mattia Falconi, Francesco Ricci, Alessandro Desideri
Here we couple experimental and simulative
techniques to characterize
the structural/dynamical behavior of a pH-triggered switching mechanism
based on the formation of a parallel DNA triple helix. Fluorescent
data demonstrate the ability of this structure to reversibly switch
between two states upon pH changes. Two accelerated, half microsecond,
MD simulations of the system having protonated or unprotonated cytosines,
mimicking the pH 5.0 and 8.0 conditions, highlight the importance
of the Hoogsteen interactions in stabilizing the system, finely depicting
the time-dependent disruption of the hydrogen bond network. Urea-unfolding
experiments and MM/GBSA calculations converge in indicating a stabilization
energy at pH 5.0, 2-fold higher than that observed at pH 8.0. These
results validate the pH-controlled behavior of the designed structure
and suggest that simulative approaches can be successfully coupled
with experimental data to characterize responsive DNA-based nanodevices.