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

Abstract

The self-assembly of short amphiphilic peptides F_mD_n and F_mK_n 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 μs-scale simulation, FD and FK only form loose polymeric clusters. Upon increasing the length of Phe residues in F_mD and F_mK (m = 2 to 4), larger and more stable micelles are formed. F_mK and F_mD prefer to assemble into quasi-spherical and sheet-like micelles, respectively. For F₃K_n (n = 2 to 8) and F₆K_n (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 F₃K_n and F₆K_n. 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.