(647a) (Invited Talk) Directed Discovery of Functional Peptide Modalities with Dynamic Conformations

All life forms share canonical sets of monomeric building blocks –amino acids that through sequence specific polymerization and non-covalent interactions achieve a bewildering array of functions. While functional proteins and peptides with stable folds can increasingly be designed and rationally modified, there is only a limited understanding of the compositional and organizational principles that dictate chemical functionality in peptides with flexible structures and dynamic conformations relevant to functions such as bio-molecular recognition, environment-responsive conformations and enzyme-like catalysis.

We use integrated experimental and computational methods to search and map the peptide interaction space for molecular self-assembly and demonstrate a variety of new functions. First, we demonstrate the design of tripeptide conformations with dynamic conformations that display dynamic fluorescence properties. Second, we show supramolecular tripeptide crystals display fully reversible and non-linear lattice deformation upon changes in humidity. These mechanically tough, yet flexible peptide nanostructures that can exert significant forces and hold promise as efficient actuators for energy harvesting, adaptive materials, and soft robotics. In a third approach, we use reversible exchange of functionally degenerate peptide mixtures to produce populations of thousands of dynamically exchanging short oligopeptides with an expansive chemical diversity. When these libraries are exposed to target molecules, exemplified by ATP, adaptive sequence amplification and compositional redistribution towards longer and more complex sequences is observed, thus gaining direct insights into conformation-driven sequence selection. Collectiviely, our approaches provide a new way of studying scenarios relevant to the chemical origins of life and design of functional peptide modalities.