(189b) Dynamic Peptide Assemblies for Sensing Applications

Biological molecules are inherently dynamic, and the ability of these macromolecules to fluctuate and explore conformation space leads to the ability of some proteins to 'break the speed limit' set by diffusion. For example, the kinetics of association between transcription factors and DNA is exceptionally fast, exceeding the maximum limit set by diffusion by 100 fold. This non-intuitive effect of structural fluctuations defines the association kinetics, and, using this mechanism, one can conceptualize the design of biological molecules in a different light, where peptides rapidly respond to the environment with structural changes. We have designed a peptide with switchable surface activity, where the folded form (á-helical) of the peptide is amphiphilic and the unfolded form is not. The primary structure of a peptide is designed in such a way that upon folding the hydrophobic and hydrophilic domains become spatially disjoint, leading to amphiphilic behavior. The ensemble average population of folded states depends on binding to a specific sequence of DNA. The secondary structure has been characterized by using circular dichroism spectropolarimetry, and we show that the peptide has a transient secondary structure as a function of binding. We believe that this work can lead to an important new class of tunable surface-active molecules. Engineering dynamic molecules, where surface-activity is coincident with the inherent specificity, will have far-reaching benefits for the design of biomimetic tools, particularly in scenarios where fast rates and selective binding are essential.