Filaments Under Force: A Computational Molecular-Scale Investigation Of Type Iv Pili From Multiple Organisms

Type IV pili (T4P) are biopolymers comprised of many protein subunits called pilin. These pilin subunits are not covalently bonded to one another, however remarkably T4P filaments are very strong and flexible. T4P emanate from the surface of prokaryotic cells and are utilized for many functions, including biofilm formation, surface adhesion, motility, and infection. The recent cryo-EM based structures for T4P from Escherichia coli, Neisseria meningitidis, Pseudomonas aeruginosa, and Neisseria gonorrhoeae have provided unprecedented insights into the structures of these filaments. However, although the structures of T4P are known, the dynamics of these filaments at the molecular scale at equilibrium and under tensile forces is not well characterized. In this work we provide an overview of our research into these various T4P filaments and their constituent pilin monomers under force. Specifically we carried out steered molecular dynamics simulations using a multiscale approach encompassing all-atom simulations and two levels of coarse-grained simulation. We have analyzed the changes in secondary structure of pilin subunits, global changes in filament architecture, and calculated the Young's modulus of each of the different T4P filaments. By drawing comparisons between all of these filament systems, we are able to obtain a broader picture of T4P dynamics than experimental structures alone can provide. In particular, we observe elongation of the alpha helix region of pilin subunits in each of these systems, which has been previously attributed to T4P flexibility and strength.