Many battles of bacterial infection and immune response are played out in biological membranes. For example, anti-microbial peptides have the capacity to partition into the membrane of gram-negative bacteria, which may induce its permeabilization. Likewise, the interaction of amyloid-forming peptide oligomers with membranes is thought to play a role in the neurotoxicity of severe degenerative pathologies such as Alzheimer’s and Parkinson’s diseases. Despite the importance of these processes to human health, elucidating the molecular mechanisms underlying the interaction of peptides and proteins with lipid membranes has remained challenging. I will show how the combination of high-performance computing with efficient sampling algorithms makes it possible to access length- and time-scales relevant to the structure and function of peptides and proteins in membrane mimetics and lipid bilayers at the atomic level of detail. I will present recent and ongoing molecular simulation studies aimed at characterizing the self-organization of amyloidogenic peptides at membrane-water interfaces and the action of a structurally-disordered antimicrobial peptide, indolicidin, on lipid bilayers.
