Coarse-Grained Simulations of the Asymmetric Mechanical Response of MS2 Bacteriophage

AFM nanoindentation is a powerful technique to characterize mechanical properties of individual virus particles. Our AFM nanoindentation experiments on MS2 virions discovered two distinct deformation pathways that strongly correlate with the orientation of the virion. To reveal the mechanisms underlying the two deformation pathways, we developed a coarse-grained model of MS2 capsid and genome that is informed by relatively short equilibrium all-atom MD simulations, with capsid proteins modeled as shape-preserving bead networks and RNA genome as an elastic polymer. Using this model to computationally perform AFM nanoindentation allows examination of the impact of genome geometry and capsid interactions on the deformation pathway. Additionally, it facilitates exploration of factors that may quantitatively influence experimental outcomes, such as AFM tip geometry and effective spring constant. In summary, the coarse-graining methods described here can provide valuable insights into virion deformation processes happening at relatively long timescales, complementing experiments.