Translocation of Biopolymers Through Protein Nanopores: Mechanistic Insights from MD Simulations

Abstract

The translocation of biopolymers through nanopores is a ubiquitous process in biology. In recent years, inspired by biology, some of these processes have been manipulated for applications in bionanotechnology, e.g. as stochastic sensors and potential DNA sequencing devices. To date research into such protein nanopores has largely focused on α-hemolysin (αHL), a transmembrane exotoxin from S. aureus. In the present study, we have developed simplified models of the wildtype αHL pore and its mutants, in order to study the translocation dynamics of DNA and peptides under the influence of an applied electric field.We show that interactions between rings of cationic amino acids and DNA backbone phosphates result in meta-stable tethering of nucleic acid molecules within the pore, leading us to propose a “binding and sliding” mechanism for translocation. We also observe folding of DNA into non-linear conformational intermediates during passage through the confined nanopore environment, helping to rationalize experimentally determined trends in residual current and translocation efficiency for αHL and its mutants. Finally, we explore the translocation of peptides (both helical and extended) through our model pores as a model of protein transport.