Structural resolution of switchable states of a de novo peptide assembly

Abstract De novo protein design is advancing rapidly. However, most designs are for single states. Here we report a de designed peptide that forms multiple ?-helical-bundle states accessible and interconvertible under the same conditions. Usually in such amphipathic ? helices associate to form compact structures with consolidated hydrophobic cores. recent rational computational have delivered open ?-helical barrels functionalisable cavities. By placing glycine judiciously helical interfaces of an barrel, obtain both crystal. Molecular dynamics simulations indicate free-energy landscape interconverting Together, these findings suggest frustrated system which steric interactions maintain barrel effect drives complete collapse traded-off. Indeed, addition co-solvent can bind within affects switch between silico experimentally.