Abstract
AbstractMolecular simulations have played an instrumental role in uncovering the structural dynamics and physical properties of virus capsids. In this work we move beyond equilibrium physicochemical characterization of a virus system to study a stage of the infection process which is required for viral proliferation. Despite many biochemical and functional studies, the molecular mechanism of host cell entry by non-enveloped viruses remains largely unresolved. Flock House Virus (FHV) is model system for non-enveloped viruses and is the subject of the current study. FHV infects through the acid-dependent endocytic pathway, where low pH triggers externalization of membrane disrupting (γ) peptides from the capsid interior. Employing all-atom equilibrium and enhanced sampling simulations, the mechanism and energetics of γ peptide liberation and the effect of pH on this process is investigated. Our computations agree with experimental findings and reveal nanoscopic details regarding the pH control mechanism which are not readily accessible in experiments.
Publisher
Cold Spring Harbor Laboratory
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