Interactions of alpha-helices with lipid bilayers: a review of simulation studies

Membrane proteins, of which the majority seem to contain one or more alpha- helix, constitute approx. 30% of most genomes. A complete understanding of the nature of helix/bilayer interactions is necessary for an understanding of the structural principles underlying membrane proteins. This review desc ribes computer simulation studies of helix/bilayer interactions. Key experi mental studies of the interactions of alpha-helices and lipid bilayers are briefly reviewed. Surface associated helices are found in some membrane-bou nd enzymes (e.g. prostaglandin synthase), and as stages in the mechanisms o f antimicrobial peptides and of pore-forming bacterial toxins. Transmembran e alpha-helices are found in most integral membrane proteins, and also in c hannels formed by amphipathic peptides or by bacterial toxins. Mean field s imulations, in which the lipid bilayer is approximated as a hydrophobic con tinuum, have been used in studies of membrane-active peptides (e.g, alameth icin, melittin, magainin and dermaseptin) and of simple membrane proteins ( e.g. phage Pf1 coat protein). All atom molecular dynamics simulations of fu lly solvated bilayers with transmembrane helices have been applied to: the constituent helices of bacteriorhodopsin; peptide-16 (a simple model TM hel ix); and a number of pore-lining helices from ion channels. Surface associa ted helices (e.g. melittin and dermaseptin) have been simulated, as have al pha-helical bundles such as bacteriorhodopsin and alamethicin. From compari son of the results from the two classes of simulation, it emerges that a ma jor theoretical challenge is to exploit the results of all atom simulations in order to improve the mean field approach. (C) 1999 Elsevier Science B.V . All rights reserved.