The Role of Hydrophobicity in the Self-assembly of PDI-peptides*

Perylene Diimide (PDI) - peptide derivatives are ideal for the design of switchable
self-assembling electronic biomaterials. Predicting the self-assembled structures
of peptide-based materials from the amino acid sequence is difficult due to the wide
array of chemical properties exhibited by peptides. We probe the role of two of these
properties, hydrophobicity and aromaticity, in the initial aggregation and ordering behavior
of PDI-peptides with all-atom molecular dynamics. Using a variety of clustering
analyses on a series of hydrophobic PDI-peptides, we show increasing hydrophobicity
leads to increased aggregate size with decreased ordering. Increasing aromaticity of the
peptide sequence enhances these effects due to peptide–peptide and peptide–PDI core
π-stacking interactions. To show these trends are predictive we study a series of PDI-RADA
with hydrophobic substitutions of the alanines. RADA is a self-complimentary
peptide sequence that is switchable under pH change and is dominated by electrostatic
interactions. Our work suggests hydrophobicity can be used to tune the self-assembly
of PDI-peptides.