Peptide framework for screening the effects of amino acids on assembly

Discovery of peptide domains with unique intermolecular interactions is essential for engineering peptide-based materials. Rather than attempting a brute-force approach, we instead identify a previously unexplored strategy for discovery and study of intermolecular interactions: “co-assembly of oppositely charged peptide” (CoOP), a framework that “encourages” peptide assembly by mixing two oppositely charged hexapeptides. We used an integrated computational and experimental approach, probed the free energy of association and probability of amino acid contacts during co-assembly with atomic-resolution simulations, and correlated them to the physical properties of the aggregates. We introduce CoOP with three examples: dialanine, ditryptophan, and diisoleucine. Our results indicated that the opposite charges initiate the assembly, and the subsequent stability is enhanced by the presence of an undisturbed hydrophobic core. CoOP represents a unique, simple, and elegant framework that can be used to identify the structure-property relationships of self-assembling peptide-based materials.