Computational Study of Cytolytic Peptides: Monomeric-Oligomeric Structures and Ligand Interactions

摘要

We have mostly followed our initial plan described in the Statement of Work to investigate membrane disrupting peptide dynamics and membrane interactions. In the first year of research, we have focused on two systems (Protegrin-1, Defensin). The major progresses have been made in PG-1 membrane interactions, and the defensin oligomerization also has preceded well. The important scientific finding during the research period is the elucidation of peptide membrane thinning mechanism. We observed that local thinning of lipid bilayers mediated by the peptide is enhanced in the lipid bilayer containing POPG, consistent with experimental results of selective membrane targeting. The conformational dynamics of Protegrin-1, especially the highly charged - hairpin turn region are found to be mostly responsible for disturbing membrane. Even though the eventual membrane disruption requires Protegrin-1 oligomer, our simulations clearly show the first step of the monomeric effects. The thinning effects in the bilayer should relate to pore/channel formation in lipid bilayer and thus responsible for further defects in the membrane caused by oligomer. These results reveal first time how a peptide in -hairpin conformation (rather than conventional -helical structure) can disrupt membrane structure. 15.