A Comparative Study of Melittin and Magainin 2 Peptides Inserted into Pores in Lipid Bilayers: Computer Simulations

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Interactions of antimicrobial peptides (AMP) with lipid bilayers and AMP formed pores are extensively studied to understand their mechanism of action. We focus on two AMPs Melittin and Magainin 2. Melittin is a well-documented AMP known to form toroidal pores, however questions exists about the arrangement of the peptides in the pore and their secondary structure. In case of Magainin 2, although one of the most studied AMP, even the existence of the toroidal pore was recently questioned. We present here a computational study that compares model pores formed by Melittin and Magainin 2 to investigate the preference for the formation of a toroidal pore and the factors that favor this preference. Four pores with different arrangement of peptides and different helicity are constructed for both Melittin and Magainin 2: symmetric less-helical, asymmetric less-helical, symmetric helical and asymmetric helical. Each pore has four peptides: if the C-termini of all the four peptides are anchored to one of the lipid leaflets the arrangement is asymmetric. If the C-termini are distributed evenly to both leaflets the arrangement is symmetric. One set of pores was constructed with the helical crystal structure of the peptides and the other with a less helical structure. We observe that the pore containing four less-helical Melittins in a symmetric arrangement is toroidal. A pore containing Magainin peptides, although permitting the flow of water, does not produce bending of the lipid head groups and hence is not toroidal. We propose that the difference in charge distribution along the peptides Melittin and Magainin 2 can explain our observation.