Molecular dynamics and (2)H-NMR study of the influence of an amphiphilic peptide on membrane order and dynamics

A molecular dynamics simulation of a fully hydrated model membrane consisting of 12 molecules of 1, 2-dimyristoyl-sn-glycero-3-phosphocholine, one amphiphilic peptide with the sequence acetyl-Lys-Lys-Gly-Leu(16)-Lys-Lys-Ala-amide, and 593 water molecules was performed for 1.06 ns (Belohorcova, K., J. H. Davis, T. B. Woolf, and B. Roux. 1997. Biophys. J. 73:3039-3055). The analysis presented here is primarily focused on the phospholipid component and the results are compared with experimental (2)H-NMR studies of the lipid component of mixtures of the same peptide and lipid at a molar ratio of 1:32, and with earlier studies of closely related peptide/lipid mixtures. The phospholipid chain and headgroup isomer populations and isomerization rates compare favorably with previous simulations and experimental measurements. Of particular interest is the effect of the peptide on the phospholipid headgroup and hydrocarbon chain orientational order calculated from the simulation, which also agree well with experimental measurements performed on this and closely related systems. Comparison of the experimental results with the simulations not only shows that there is significant agreement between the two methods, but also provides new insight into the effect of the peptide on the lipid dynamics. In particular, these results confirm that a membrane spanning peptide has little effect on lipid chain order, and bilayer thickness if its hydrophobic length closely matches the lipid hydrocarbon thickness. In addition, we find that the peptide can have a strong ordering effect if it is longer than the lipid hydrophobic thickness.