Gating-like Motions and Wall Porosity in a DNA Nanopore Scaffold Revealed by Molecular Simulations.
Recently developed synthetic membrane pores composed of folded DNA enrich the current range of natural and engineered protein pores and of nonbiogenic channels. Here we report all-atom molecular dynamics simulations of a DNA nanotube (DNT) pore scaffold to gain fundamental insight into its atomic structure, dynamics, and interactions with ions and water. Our multiple simulations of models of DNTs that are composed of a six-duplex bundle lead to a coherent description. The central tube lumen adopts a cylindrical shape while the mouth regions at the two DNT openings undergo gating-like motions which provide a possible molecular explanation of a lower conductance state observed in our previous experimental study on a membrane-spanning version of the DNT (ACS Nano 2015, 9, 1117-26). Similarly, the central nanotube lumen is filled with water and ions characterized by bulk diffusion coefficients while the gating regions exhibit temporal fluctuations in their aqueous volume. We furthermore observe that the porous nature of the walls allows lateral leakage of ions and water. This study will benefit rational design of DNA nanopores of enhanced stability of relevance for sensing applications, of nanodevices with tunable gating properties that mimic gated ion channels, or of nanopores featuring defined permeation behavior.
Department of Biochemistry, University of Oxford , South Parks Road, Oxford OX1 3QU, Oxford, United Kingdom.
Vishal
V
Maingi
Department of Biochemistry, University of Oxford , South Parks Road, Oxford OX1 3QU, Oxford, United Kingdom.
Mickaël
M
Lelimousin
Department of Chemistry, Institute of Structural Molecular Biology, University College London , London WC1H 0AJ, England, United Kingdom.
Stefan
S
Howorka
Department of Biochemistry, University of Oxford , South Parks Road, Oxford OX1 3QU, Oxford, United Kingdom.
Mark S P
MS
Sansom
D004247:DNA / Q000737:chemistry*; D004058:Diffusion; D007477:Ions; D056004:Molecular Dynamics Simulation; D009038:Motion; D058608:Nanopores; D043942:Nanotubes / Q000737:chemistry; D009690:Nucleic Acid Conformation; D010316:Particle Size; D016062:Porosity; D014867:Water / Q000737:chemistry
D007477:Ions; D014867:Water; D004247:DNA
DNA origami; diffusion; gating; molecular dynamics; nanopore