Nature has almost certainly only shown us a glimpse of what is possible structurally and functionally with polypeptide chains. To help us explore past the confines of natural protein structures, and into what has been termed the dark matter of protein space, we have developed a toolkit of de novo peptides.1 These can be used as building blocks for the rapid construction of new protein structures and supramolecular assemblies. This talk will demonstrate the utility of this approach to make nanoscale protein pores,2,3 and peptide-based nanocages.4 Potential applications of these structures and materials span nanoscience, synthetic biology, and biotechnology. (1) A basis set of de novo coiled-coil peptide oligomers for rational protein design and synthetic biology. Fletcher, J. M.; Boyle, A. L.; Bruning, M.; Bartlett, G. J.; Vincent, T. L.; Zaccai, N. R.; Armstrong, C. T.; Bromley, E. H. C.; Booth, P. J.; Brady, R. L.; Thomson, A. R.; Woolfson, D. N. ACS Synth. Biol. 2012, 6, 240–250. (2) A de novo peptide hexamer with a mutable channel. Zaccai, N. R.; Chi, B.; Thomson, A. R.; Boyle, A. L.; Bartlett, G. J.; Bruning, M.; Linden, N.; Sessions, R. B.; Booth, P. J.; Brady, R. L.; Woolfson, D. N. Nat. Chem. Biol. 2011, 7, 935–941. (3) Computational design of water-soluble α-helical barrels. Thomson, A. R.; Wood, C. W.; Burton, A. J.; Bartlett, G. J.; Sessions, R. B.; Brady, R. L.; Woolfson, D. N. Science 2014, 346, 485–488. (4) Self-assembling cages from coiled-coil peptide modules. Fletcher, J. M.; Harniman, R. L.; Barnes, F. R. H.; Boyle, A. L.; Collins, A.; Mantell, J.; Sharp Antognozzi, T. H.; Booth, P. J.; Linden, N.; Miles, M. J.; Sessions, R. B.; Verkade, P.; Woolfson, D. N. Science 2013, 340, 595–599.

Exploring the dark matter of protein space through de novo peptide design

251st National Meeting (2016)

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