(158aa) The Role of Lipids on Transmembrane Protein Interactions in Viral Infections

We are increasingly aware of the relevance of specific lipid-protein interactions in cellular processes; not only to maintain a healthy cell, but also facilitating disease progression. In the context of viral infections, we present a molecular dynamics study that examines the interactions of the influenza A M2 ion channel in a realistic membrane model. This tetrameric viroporin is the smallest of its kind and is key for viral replication. Similar viroporins are found in other viruses such as HIV-1 (Vpu), hepatitis C (p7), and coronaviruses like the newly identified SARS-CoV-2 (E). Our simulations aim to characterize molecular interactions at the interface between viral proteins and endogenous cell membrane components. Namely, to quantify the changes in the local membrane environment due to the formation of viroporins, i.e. membrane structural and mechanical properties including lipid bilayer order and thickness, which in turn modulate channel activity. In examining this model, we also aim to identify conserved effects of viroporins on host membranes. The data from these atomistic simulations will later serve to improve a coarse-grain model of influenza A viral dynamics that accounts for membrane response to activity and aggregation of these channels.