(35d) Peptide Framework for Screening the Effects of Amino Acids on Assembly

Discovery of small peptide domains with unique intermolecular interactions is essential for engineering new materials. Such discovery via screening all possible permutations of amino acids is impractical, while editing known peptides to create simple variations of it for a particular end product limits the achievable properties. Rather than attempt a brute-force approach, we instead combine these approaches and highlight the utility of “co-assembly of oppositely charged peptide” (CoOP), a framework that ‘encourages’ the assembly into a one-dimensional structure. CoOP form of only six amino acids, two of which form a “substitution domain” to study and correlate the influence of different amino acids on free energy differences of peptide aggregates, assembly kinetics, mechanism, and mechanical properties of the end product. A remarkable range of properties were observed via substitution of dialanine, ditrytophan, and diisoleucine. Diisoleucine assembles into fibrils instantaneously in water at less than 25μM (0.002 w%) and form a gel at 10 mM (<1 w%) at 200 Pa storage modulus, while dialanine system does not form fibrils in the concentrations studied. Importantly, both molecular simulations and experimental results indicate that salt bridges between the opposite charges initiate the assembly, and the subsequent stability is enhanced by the presence of an undisturbed hydrophobic core. We use an integrated computational and experimental approach to analyze the properties of CoOP with substituted domains. We probed the free energy of association and probability of amino acid contacts during co-assembly with atomic-resolution simulations and correlate them to the physical properties of the end product. Such correlation could happen as CoOP represents a unique, simple and elegant assembly framework, provides discovery and high-resolution examination of the effects of minimal substitutions of molecular interactions on peptide assembly and end-product proper-ties. CoOP framework can be used to identify the structure - property interactions of self-assembling peptide-based biomaterials.