Microscopic insight into self-assembly of amphiphilic peptides: the influence of hydrophilic residues

Unveiling the self-assembly mechanism of amphiphilic peptides is crucial for the development of functional supramolecular biomaterials. The chemical properties of hydrophilic amino acids play an essential role in this process. Our multiscale molecular dynamics (MD) simulations indicated that the hydrophilic residue, threonine (T), is an excellent candidate to balance the hydrophobicity of the peptide, which could enhance the self-assembly ability of the peptide. In addition, simulations demonstrated that the number of hydrogen bonds within peptide assemblies did not correlate directly with their stability. Preventing hydrophilic side chains from disrupting the hydrogen bond network between the peptide backbones can improve self-assembly stability. Together with the experimental validation, we believe that T is a promising amino acid to balance the hydrophobicity of amphiphilic peptides. This work highlights the importance of hydrophilic amino acids in peptide self-assembly, which could be further utilized for designing amphiphilic peptides with different functions.