Molecular dynamics simulations of the insertion of two ideally amphipathic lytic peptides LK 15 and LK 9 in a 1,2-dimyristoylphosphatidylcholine monolayer

Abstract

We present here the results of 1-ns molecular dynamics (MD) simulations of two ideally amphipathic lytic peptides, namely LK 15 and LK 9, in a 1,2-dimyristoylphosphatidylcholine monolayer with two different cross-sectional areas per lipid of 80 Å 2 (loose film) and 63 Å 2 (tight standard film). These peptides are lytic, ideally amphipathic with a minimalist composition L i K j and the following sequences: H 2N-KLLKLLLKLLLKLLK-CO-Ph for LK 15 and H 2N-KLKLKLKLK-CO-Ph for LK 9. From experimental data, LK 15 exhibits an α-helical secondary structure, whereas LK 9 was found to form antiparallel β-sheets at the interface of a DMPC monolayer. Whatever the specific lipid surface is, the two peptides exhibit very different behavior: the α-helix inserts deeply into the monolayer whereas the β-sheeted peptide stays at the surface within the upper polar part of the monolayer. In all cases, a loose monolayer (80 Å 2) results in noticeable artifacts whereas a monolayer with standard specific surface leads to very reliable behavior well in accordance with experimental data. Despite their different insertion depth, the two peptides exhibit identical lytic efficiency. This is very likely a direct consequence of the very strong Van der Waals interactions between the fatty alkyl chains of the lipids and the highly lipophilic lower part of the peptide, resulting in an identical thinning of the two monolayers.