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.

Structure and dynamics of an amphiphilic peptide in a lipid bilayer: a molecular dynamics study.

A molecular dynamics simulation of a simple model membrane system composed of a single amphiphilic helical peptide (ace-K2GL16K2A-amide) in a fully hydrated 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayer was performed for a total of 1060 ps. The secondary structure of the peptide and its stability were described in terms of average dihedral angles, phi and psi, and the C alpha torsion angles formed by backbone atoms; by the average translation per residue along the helix axis; and by the intramolecular peptide hydrogen bonds. The results indicated that residues 6 through 15 remain in a stable right-handed alpha-helical conformation, whereas both termini exhibit substantial fluctuations. A change in the backbone dihedral angles for residues 16 and 17 is accompanied by the loss of two intramolecular hydrogen bonds, leading to a local but long-lived disruption of the helix. The dynamics of the peptide was characterized in terms of local and global helix motions. The local motions of the N-H bond angles were described in terms of the autocorrelation functions of P2[cos thetaNH(t, t + tau)] and reflected the different degrees of local peptide order as well as a variation in time scale for local motions. The chi1 and chi2 dihedral angles of the leucine side chains underwent frequent transitions between potential minima. No connection between the side-chain positions and their mobility was observed, however. In contrast, the lysine side chains displayed little mobility during the simulation. The global peptide motions were characterized by the tilting and bending motions of the helix. Although the peptide was initially aligned parallel to the bilayer normal, during the simulation it was observed to tilt away from the normal, reaching an angle of approximately 25 degrees by the end of the simulation. In addition, a slight bend of the helix was detected. Finally, the solvation of the peptide backbone and side-chain atoms was also investigated.