ABSTRACT: I will present our studies of the structure and mechanism of two membrane proteins, the influenza virus M2 protein and the paramyxovirus PIV5 F fusion peptide. Solid-state NMR spectroscopy provides a powerful tool to determine not only the conformation of peptides and proteins bound to phospholipid bilayers, but also the backbone and sidechain dynamics, protein-ligand interaction, protein-lipid interaction, and oligomeric structure. For the M2 proton channel, exchange NMR, 2D correlation spectroscopy, and distance measurements revealed the proton transfer kinetics, proton dissociation equilibria, and hydrogen bonding between water and a key histidine residue. Our studies lead to detailed insights into the drug inhibition mechanism and proton conduction mechanism of M2, and suggest the functional roles of multiple conformations of the PIV5 fusion peptide.