Highly Driven Polymer Translocation in the Presence of External Constraints: Simulations and Theory

Abstract

DNA sequencing via nanopore translocation was a pipedream two decades ago. Today, biotech companies are releasing commercial devices. Yet many challenges still hover around the simple concept of threading a long DNA molecule through a small nanoscopic pore with the aim of extracting the DNA’s sequence along the process. In this thesis I use computer simulations to create what are in essence virtual pro- totypes for testing design ideas for the improvement of nanopore translocation devices. These ideas are based on the general concept of modifying the average shape of the initial DNA conformations. This is done, for example, by introducing new geometrical features to the nanopore’s surrounding or by the means of some external force. The goal of these simulations is not just to test design improvements, but also to systematically deconstruct the physical mechanisms involved in the translocation process. The roles of pore friction, initial polymer conformations, monomer crowding on the trans- side of the membrane, Brownian fluctuations, and polymer rigidity can, with careful consideration, be essentially muted at will. Computer simulations in this sense play the role of a sandbox in which the physics can be tinkered with, in order to assess and evaluate the magnitude of certain approximations found in theoretical modelling of translocation. This enables me to construct theoretical models that contain the necessary features pertaining to the different designs tested by simulations. The work presented here is thus constituted of both Langevin Dynamics simulations and adaptations of the Tension-Propagation theory of polymer translocation when the polymer is subject to the various test conditions.