Simulation studies of the interaction of antimicrobial peptides and lipid bilayers

Experimental studies of a number of antimicrobial peptides are sufficiently detailed to allow computer simulations to make a significant contribution to understanding their mechanisms of action at an atomic level. In this rev iew we focus on simulation studies of alamethicin, melittin, dermaseptin an d related antimicrobial, membrane-active peptides. All of these peptides fo rm amphipathic alpha-helices. Simulations allow us to explore the interacti ons of such peptides with lipid bilayers, and to understand the effects of such interactions on the conformational dynamics of the peptides. Mean fiel d methods employ an empirical energy function, such as a simple hydrophobic ity potential, to provide an approximation to the membrane. Mean field appr oaches allow us to predict the optimal orientation of a peptide helix relat ive to a bilayer. Molecular dynamics simulations that include an atomistic model of the bilayer and surrounding solvent provide a more detailed insigh t into peptide-bilayer interactions. In the case of alamethicin, all-atom s imulations have allowed us to explore several steps along the route from bi nding to the membrane surface to formation of transbilayer ion channels. Fo r those antimicrobial peptides such as dermaseptin which prefer to remain a t the surface of a bilayer, molecular dynamics simulations allow us to expl ore the favourable interactions between the peptide helix sidechains and th e phospholipid headgroups. (C) 1999 Elsevier Science B.V. All rights reserv ed.