  Relatively short peptides, such as toxins and antimicrobial-peptides, are
known to insert themselves into cell membranes. On the basis of simple
bead-spring models for the membrane lipids, the peptide, and water, detailed
processes of the peptide insertion is investigated by molecular dynamics
simulation; our special concern is in the highly cooperative motions of
membrane lipids and the peptide. Our model lipid has a head group of three
hydrophilic beads and a tail of seven hydrophobic beads, while the model
peptide is a block-copolymer made of hydrophilic and hydrophobic blocks, with
total length of 200 beads. In addition, each water molecule is represented by a
single bead which has considerably larger interaction energy. We first confirm
that our present lipid model can support spontaneous formation of bilayers in
water. Then we place the model peptide near the bilayers and monitor the
microscopic process of the adsorption, insertion, and translocation of the
peptide. When the peptide molecule is set free to interact with the membrane,
the hydrophobic blocks of the peptide strongly favor intimate contact with the
lipid tails. This strong attractive interaction gives rise to a severe membrane
perturbation, which leads to the formation of a pore, though short-lived, in
the membrane. It is found that the side-surface of the pore is almost covered
with the hydrophilic heads of the lipids, which seems to help the hydrophilic
blocks of the peptide translocate across the membrane. We also monitor the rate
of flip-flop inversion of the directions of lipids, and we find it markedly
increases during the peptide contact and insertion. The peptide
insertion/translocation, the formation of membrane pore, and the flip-flop
motions of the lipids are thus found to be closely interconnected.
