Title:  In Situ Dynamics Reveal Unseen Vulnerabilities of Viral Glycoproteins
Abstract:  Viral glycoproteins are important targets for vaccine and drug design. I will discuss our efforts to provide never-before-seen views of these amazing molecular machines, for both SARS-CoV-2 and influenza. For the latter, we investigated the dynamics of influenza glycoproteins in a crowded protein environment through mesoscale all-atom molecular dynamics simulations of two evolutionary-linked glycosylated influenza A whole-virion models. Our simulations reveal and kinetically characterize three main molecular motions of influenza glycoproteins: NA head tilting, HA ectodomain tilting, and HA head breathing. From an immunogenic point of view, the glycoproteins’ accentuated conformational plasticity observed in our simulations has unveiled their full vulnerabilities, exposing epitopes that otherwise would not be accessible or would be sterically occluded. Our work therefore highlights the importance of exploring and characterizing in situ dynamics of proteins in their native, crowded environments.