(420aj) Self-Assembly of Amphiphilic Peptide (AF)6H5K15: Roles of Hydrophobic and Hydrophilic Residues

A molecular dynamics simulation study is reported to investigate the roles of hydrophilic and hydrophobic residues in the self-assembly of (AF)₆H₅K₁₅ peptide derivatives. The peptide, as well as water and counterions, are represented by the MARTINI coarse-grained model. The assembly is observed to follow a three-step process: formation of small clusters, large clusters and micelles. With increasing length of hydrophilic Lys residues in (AF)₆H₅K_n (n = 10, 15, 20 and 25), assembly capability is found to be reduced with the formation of smaller micelles or the presence of individual peptide chains. Upon replacing Ala by more hydrophobic Phe in A_mF_nH₅K₁₅ (m + n = 12), larger micelles are formed. With increasing length of hydrophobic Phe residues in F_nH₅K₁₅ (n = 4, 8, 12 and 16), micelle size increases and the morphology shifts from spherical to fiber-like. The simulation study provides mechanistic insight into the crucial roles of hydrophilicity and hydrophobicity in the assembly of (AF)₆H₅K₁₅ derivatives;  it reveals that assembly capability is reduced by increasing hydrophilicity, whereas increasing hydrophobicity leads to morphology transition.