Aggregation of Lysozyme in the Presence of a Mixed Bilayer of POPC and POPG

[Image: see text] Understanding the molecular mechanisms by which amyloidogenic proteins interact with membranes is a challenging task. Amyloid accumulates from many human diseases have been observed to contain membrane lipids. In this work, coarse-grained molecular dynamics simulations have been used to inspect hen egg white lysozyme (HEWL) aggregation and membrane association in the presence of a pure POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) bilayer and a POPC and POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol) mixed bilayer. It was observed that, in both cases, two HEWLs formed aggregates. In the presence of a mixed bilayer, after aggregation, the aggregated system started to interact with the membrane. It has been found that one of the lysozymes which came closer to the mixed bilayer unfolded more. The process of the initial insertion of an aggregated system in the mixed bilayer has been analyzed. The structural rearrangements of the protein and lipids were analyzed as well along the course of the simulation. Although with a pure POPC bilayer, aggregation was observed, the aggregated system moved away from the membrane. We believe that our study will provide considerable insights into lysozyme aggregation in the presence of a membrane environment.