The Structure of a Melittin Stabilized Toroidal Pore

Abstract

Melittin is a 26-residue lytic peptide that is more effective at degrading zwitterionic membranes than membranes containing anionic lipids. At high peptide/lipid ratios there is evidence that melittin forms toroidal pores lined by peptides and lipid head groups, as opposed to the “barrel-stave” model where transmembrane peptides fully line the pore in a cylindrical manner. However, the detailed structure of these pores remains unknown. Microsecond all atom molecular dynamics simulations of a closely packed tetramer were performed in an effort to determine a well-equilibrated stable pore structure. The trajectory in DMPC shows early formation of a toroidal pore which remains stable for the remainder of the 9 μs simulation. An additional 9 μs simulation from the same starting structure was performed in membranes containing 25% anionic lipids (DMPG). In that case, despite a limited initial entry of water and head groups in the membrane hydrophobic core, no stable pore was observed.