Action of membrane-active peptides on explicit lipid bilayers. Role of specific peptide-lipid interactions in membrane destabilization

Motivation: Membrane-active peptides play a crucial role in numerous cell processes, such as fusion, transport of therapeutic compounds, disturbance of integrity of membranes, and others. Many of them act as highly specific and efficient drugs and, therefore, attract growing interest for biomedical applications. Because of experimental difficulties with characterization of their spatial structure and mode of membrane binding, essential attention is given now to molecular modeling techniques. Results:The present work sums up our recent results on molecular dynamics (MD) simulations of binding of several membrane active (fusogenic, antimicrobial and cell penetrating) peptides (MAP) to hydrated lipid bilayers differing in length, saturation degree of acyl chains, chemical nature and/or charge of headgroups. The character of "membrane response" may significantly vary depending on the peptide type and it target membranes. However, a number of common phenomena in MAP-membrane interactions can be outlined. The mode of peptide binding to membrane correlates with a rate of membrane destabilization - deeper insertion of a peptide leads to the more prominent effect. The "membrane response" induced by a peptide may be caused by formation of specific peptide-lipid complexes. Relationships between character of interactions of peptides with membranes and the mechanism of their action are also discussed.