Nucleotide Dynamics During Flossing of Polycation-DNA-Polycation through a Nanopore using Molecular Dynamics

Abstract

The full potential of solid state nanopores is yet to be realized for genome sequencing. Due to its robustness it can handle strong voltage amplitude and frequency. The effect of strong alternating voltage on the dynamics of nucleotides during translocation has been explored. We proposed a setup consisting of single stranded DNA covalently linked with symmetric polycations at both ends fashioned after the proposal of Kasianowicz. 1 Such a setup allows for repeated back and forth motion of the DNA along the nanopore (1.45 nm diameter and 1.53 nm thick) by simply switching the voltage polarity if the polycation tail is sufficiently long ([≥] 10) and the applied voltage is below 0.72 volts, but the average residence time of the nucleotides are too small to be of any practical use (6-30 ns). When alternating voltage of higher frequency is applied, it enhances the average residence time of the nucleotides by an order of magnitude to [~] 0.1 {micro}s relative to direct voltage but the individual trajectories are too stochastic. Since, we are able to collect repeated read on the dynamics of individual nucleotides, we obtained the most probable time of appearance of a nucleotide within the nanopore. With such construct we were able to get almost linear dependence of most probable time versus nucleotide index, after gaussian fitting.