title: Simulative and Experimental Characterization of a pH-Dependent Clamp-like DNA Triple-Helix Nanoswitch.
abstract: 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.
authors.affiliation: Department of Biology and ‡Department of Chemistry, University of Rome, Tor Vergata , 00173 Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Iacovelli
authors.affiliation: Department of Biology and ‡Department of Chemistry, University of Rome, Tor Vergata , 00173 Rome, Italy.
authors.forename: Andrea
authors.identifier: 0000-0002-6004-270X
authors.initials: A
authors.lastname: Idili
authors.affiliation: Department of Biology and ‡Department of Chemistry, University of Rome, Tor Vergata , 00173 Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Benincasa
authors.affiliation: Department of Biology and ‡Department of Chemistry, University of Rome, Tor Vergata , 00173 Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Mariottini
authors.affiliation: Department of Biology and ‡Department of Chemistry, University of Rome, Tor Vergata , 00173 Rome, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Ottaviani
authors.affiliation: Department of Biology and ‡Department of Chemistry, University of Rome, Tor Vergata , 00173 Rome, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Falconi
authors.affiliation: Department of Biology and ‡Department of Chemistry, University of Rome, Tor Vergata , 00173 Rome, Italy.
authors.forename: Francesco
authors.identifier: 0000-0003-4941-8646
authors.initials: F
authors.lastname: Ricci
authors.affiliation: Department of Biology and ‡Department of Chemistry, University of Rome, Tor Vergata , 00173 Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Desideri
mesh_terms: D004247:DNA / Q000737:chemistry*; D005453:Fluorescence; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D013816:Thermodynamics
chemical_list: D004247:DNA