Molecular insights into the self-assembly of short amphiphilic peptides FmDn and FmKn

The self-assembly of short amphiphilic peptides FmDn and FmKn is investigated by molecular dynamics simulation. The peptides are composed of hydrophobic phenylalanine (Phe, F), as well as hydrophilic aspartic acid (Asp, D) and lysine (Lys, K), and described by a coarse-grained MARTINI force field. Within ms-scale simulation, FD and FK only form loose polymeric clusters. Upon increasing the length of Phe residues in FmD and FmK (m = 2 to 4), larger and more stable micelles are formed. FmK and FmD prefer to assemble into quasi-spherical and sheet-like micelles, respectively. For F3Kn (n = 2 to 8) and F6Kn (n = 4 to 12), the assembly capability reduces leading to smaller micelles when the length of Lys residues increases. For the formation of quasi-spherical micelles with distinct core/shell structure, the optimal ratio of hydrophobic/hydrophilic residues is found to be 3/4 for both F3Kn and F6Kn. This simulation study provides molecular insights into the assembly process and mechanism of short peptides, and it could facilitate the development of new peptides with desired morphologies.