LmSn

Michael Wilson and Andrew Pohorille

The poly-leucine peptide was observed to fold into an -helix as it translocated from water to hexane. When do aggregates of membrane peptides form - before insertion or after? To address this question, simulations were performed on a 21-residue peptide of sequence (LSLLLSL) designed to fold into an -helix in which the serine residues form a hydrophilic face and the leucine residues form a hydrophobic face. In the nonpolar environment of a membrane, it is expected that the helices should dimerize with their leucine faces pointed outward, into the membrane core. A dimer of these peptides was prepared as a parallel, coiled-coil bundle and equilibrated in vacuum. The bundle was placed parallel to a water-hexane interface. After only 2 ns, the dimer dissociated to form monomers in which serines formed hydrogen bonds to the water (see FIGURE). When a similar coiled-coil bundle was placed perpendicular to the interface, a dimer remained stable on the time scale of the simulation. The ends of the peptides frayed as some serines formed hydrogen bonds to water, but serines in the centers of each peptide maintained strong hydrogen bonds to serines on the other peptide (see FIGURE). The free energy barriers between the perpendicular and parallel orientations of the bundle were found to be much larger than the free energy that can be surmounted by thermal fluctuations. Further simulations on the mechanism and energetics of peptide aggregation in membranes are in progress.