Simulation and modelling to develop a nanopore-based device for ricin detection

Abstract

Nanopore-based protein detection represents an exciting opportunity to develop ultrasensitive diagnostic devices that are both portable and affordable. Aptamer-encoded nanopores detect target molecules by binding to them to facilitate a corresponding blockage of ionic flow through the pore. Molecular dynamics simulations are an effective method of quantitatively and qualitatively studying key design features and mechanisms of current blockage. This work uses coarse-grained Langevin dynamics simulations to explore various aptamer-encoded nanopore systems to facilitate the design of diagnostic devices to detect the bioterror agent, ricin. The optimal signal-to-noise ratio occurred when ricin could occupy and interact in a stable manner within a pore cylinder that was similar in size, as predicted by the steric exclusion model of current blockage. Interestingly, under certain conditions, ricin also elicited ionic current selectivity. The results presented in this thesis have practical implications for device design, and the methodology is well-positioned to efficiently study related systems.