Melittin Interactions with Model Membranes : A Molecular Dynamics Study

Sammanfattning

Antimicrobial peptides are of interest as potential alternatives to conventional antibiotics. One ex- ample is melittin, a cationic and amphipathic peptide with strong interactions with lipid membranes. This project studies the structure and behavior of melittin in bulk solution and at lipid membranes of different charges using atomistic molecular dynamics simulations and an explicit water model. Neu- tral POPC and anionic POPC:POPS were used to model membrane systems to study how membrane charge influences peptide-membrane interactions. Small-angle X-ray scattering (SAXS) measurements were performed on melittin in solution. The simulations show that melittin remains flexible and disor- dered in bulk solution and does not have a stable folded structure. When introducing a lipid membrane, the peptide quickly associates with it and stays associated throughout the simulations. Membrane charge primarily affects the extent of the association; in anionic POPC:POPS membrane there is a stronger electrostatic interaction which brings melittin closer to the membrane with increased sur- face binding and compaction compared to neutral POPC bilayer. SAXS measurements on melittin in solution show how the peptide stays flexible and does not undergo any major compaction. The results in this project highlight the effect of electrostatic interactions in peptide-membrane association and shows that melittin primarily interacts with membranes through dynamic association with the membrane surface.