Ion Conductivity, Structural Dynamics and the Effective Force in DNA Origami Nanopores

Abstract

Nanopores have emerged as convenient tools for single molecule manipulation and analysis. In a typical measurement, a charged biomolecule-DNA or a protein-is transported through a narrow pore in a biological or synthetic membrane by external electric field. The presence and, in some cases, the chemical structure of the biomolecules is detected by measuring changes in the ionic current that flows through the nanopore. Recently, it has become possible to combine solid-state nanopores with self-assembled DNA nanostructures, the so-called DNA origami, into hybrid pores of advanced functionality. In such systems, a DNA origami plate partially covers the solid-state nanopore, providing both a nanopore of well-defined chemical structure and a platform for incorporation of auxiliary systems such as processive molecular motors and/or metallic nanoparticles. Here, we report molecular dynamics simulations of DNA origami nanopores that characterized the microscopic properties of such systems with unprecedented resolution. First, we built accurate all-atom models of DNA origami nanopores based on the honeycomb and square lattices and simulated the models using the molecular dynamics method. Next, we determined the ionic conductivity of different DNA origami designs by performing the simulations under applied electric field. For some square lattice designs, we observed reversible changes in the DNA origami structures responsive to the magnitude of the applied electric field. In the final set of simulations, we studied the electrophoretic transport of double-stranded DNA through DNA origami nanopores and characterized the effective force exerted by the applied field on both the permeating DNA molecule and the DNA origami structure. Our simulations demonstrate the utility of the molecular dynamics method for rational engineering of DNA origami nanopores into nanoscale sensors of advanced detection functionality.