Abstract
In this study, a combination of bioinformatics and molecular dynamics simulations is employed to investigate the partitioning behavior of different classes of antimicrobial peptides (AMPs) into model membranes. The main objective is to identify any correlations between the structural characteristics of AMPs and their membrane identification and early-stage partitioning mechanisms. The simulation results reveal distinct membrane interactions among the various structural classes of AMPs, particularly in relation to the generation and subsequent interaction with lipid packing defects. Notably, AMPs with a structure-less coil conformation generate a higher number of deep and shallow defects, which are larger in size compared to other classes of AMPs. AMPs with helical component demonstrated the deepest insertion into the membrane. On the other hand, AMPs with a significant percentage of beta sheets tend to adsorb onto the membrane surface, suggesting a potentially distinct partitioning mechanism attributed to their structural rigidity. These findings highlight the diverse membrane interactions and partitioning mechanisms exhibited by different structural classes of AMPs.