Identifying Peptide-Peptide Interactions with Lysenin Nanopores

Abstract

Bacteriophage T4 is one of the most common and complex tailed viruses from the family Myoviridae, and it infects E. coli using a highly efficient contractile genome delivery machine. Phage T4 possesses a multi-protein capsid containing the genomic DNA and a long contractile tail assembly that consists of a rigid tail tube surrounded by a six helical-stranded sheath. The tail assembly transmits the genomic DNA from the capsid to the host during injection. While the atomistic structure of phage T4 has been studied extensively using Cryo-EM and X-Ray crystallography, the dynamics of the injection process is not well understood. Questions remain regarding the energetics of injection as well as the pathway and time scale of the large conformational change of the sheath. In this study, we employ a dynamic multi-scale model to address these fundamental questions. To this end, a two-stage solution process is employed; first, a molecular dynamics (MD) simulation is carried out to estimate the elastic properties of the sheath strands. Second, a continuum model is developed for the entire-assembled T4 injection machinery using the elastic constants estimated from MD. The resulting multi-scale model simulates the dynamics of the sheath represented by six interacting helical strands that are coupled to the capsid represented by a massive cylinder. Dynamic simulations reveal the time scale, the pathway of sheath contraction, and the energetics driving the injection process. While these results are specific to T4 as an example, the resulting model and methodology may also inform the future design of nanotechnology injection devices.