Abstract
Antimicrobial peptides (AMPs) are regarded as a promising alternative to conventional antimicrobials, but their mechanism of action is not completely understood. Using long-scale molecular dynamics simulations, we investigate the behavior of two newly isolated AMPs from the Helix aspersa mucus fraction with molecular weight (MW) below 3 kDa in mono-and multicomponent solutions, prior to their engagement with the pathogenic membrane. In both instances, the peptide monomers form clusters consisting of a non-polar hydrophobic nucleus surrounded by charged and polar residues exposed to the solvent. We consider the so-formed structures to be the ideal transport and coalescence system-locking the hydrophobic uncharged residues in the cluster core prevents interaction with the eukaryotic membranes, while solvent exposed charged residues enable electrostatic interaction with the bacterial surface. In addition, the amphiphilic structure of the aggregates promotes peptide folding, which increases the local concentration of AMPs delivered to the target membrane in a functionally active conformation.