The physicochemical properties of AMPs are highly variable, and their ability to form dimers, oligomers, and larger aggregates adds complexity. These supramolecular structures can exhibit properties distinct from their monomeric forms, influencing both activity and toxicity. Initial peptide-membrane recognition is often driven by electrostatic interactions. For many peptides, this is merely the first step, while others rely entirely on surface interactions to drive activity, such as peptides that promote the formation of anionic lipid domain formation . Hydrophobicity is another important determinant for membrane interaction and is pivotal in balancing activity with toxicity. For example, reducing the hydrophobicity of peptides like Colistin , , and Gramicidin S [401] has yielded derivatives with improved therapeutic indices, supporting evidence that promiscuous insertion into zwitterionic membranes is largely hydrophobicity-driven . C-terminal amidation is a common modification that significantly influences antimicrobial and hemolytic activity by altering net charge and hydrophobicity . However, increased hydrophobicity from amidation can promote aggregation, potentially enhancing hemolytic activity . While large peptide aggregates often exhibit hemolytic properties, dimerization appears to promote antimicrobial activity . Aggregation at low peptide concentrations is frequently driven by hydrophobic interactions , but no universal causal relationship between aggregation and hemolysis has been established . In some cases, aggregation even reduces toxicity when peptide-peptide interactions shield hydrophobic domains, preventing membrane access . The membrane interactions of peptide aggregates -whether homo-or heterodimers, oligomers, or larger assemblies -can differ substantially from that of monomers. Their relative toxicity is highly case-specific. The possible missing 4.3 How MD simulations can integrate with experimental studies? causality between aggregation and hemolysis is that promiscuous membrane activity is hydrophobicity-driven, hence even non-aggregating highly hydrophobic peptides are more likely to be toxic.