Structural effects of tachyplesin I and its linear derivative on their aggregation and mobility in lipid bilayers.

We performed coarse-grained molecular dynamics simulations of tachyplesin I (TP-I), which is a β-hairpin antimicrobial peptide with two disulfide bonds, and its linearly extended derivative without disulfide bonds (TPA4) in lipid bilayers for 5μs. β-hairpin TP-I peptides tend to individually bind to the bilayer surface, while linear TPA4 peptides aggregate and form the β-strand complex on the bilayer surface, indicating the effect of the peptide structure on aggregation. Also, TPA4 more slowly diffuse along the bilayer surface than do TP-I, indicating that aggregated β-strands of TPA4 cannot diffuse as fast as individual β-hairpins of TP-I. TPA4 have the stronger charge interaction with lipid head groups than do TP-I, leading to the deeper insertion into the bilayer. These simulation results indicate that TP-I peptides tend to individually exist on the bilayer surface and thus easily diffuse along the bilayer surface, while TPA4 peptides aggregate as β-strands, which limits the lateral mobility of TPA4, leading to a strong immobilization of TPA4. These findings agree well with the experimentally observed dependence of peptide mobility on the peptide structure in membranes, as well as support experimental suggestions regarding the formation of β-strand complexes of linear TPA4 and the relationship between the peptide aggregation and mobility.