Although not extensively discussed, snapshots of the simulations indicated that the N-terminal tryptophan played a critical role in the early stages of membrane penetration. Tryptophan is a well-known membrane-penetrating residue, and its unique structural and physico-chemical properties contribute significantly to membrane disruption in various AMPs . Its membrane insertion depth is correlated with the overall hydrophobicity of the peptide, as demonstrated for Cecropin by Schlamadinger et al. , suggesting that Trp's positioning within the membrane is crucial for its function. Membrane surface destabilization was individuated as the mechanism of action also for the Legumin-derived peptides Leg1 and Leg2 . Leg2 shows a C-terminal motif WLKL similar to the N-terminal of both CM-11 and CM-15, and indeed the C-ter residues of Leg2 were confirmed to posses their energy minimum close to the membrane surface highlighting the role of Trp-containing motifs to favorably interact with the phosphate-headgroup region, even across unrelated peptides.