De novo design of protein homo-oligomers with modular hydrogen-bond network-mediated specificity

Scott E. Boyken, Zibo Chen, Benjamin Groves, Robert A. Langan, Gustav Oberdorfer, Alex Ford, Jason M. Gilmore, Chunfu Xu, Frank DiMaio, Jose Henrique Pereira, Banumathi Sankaran, Georg Seelig, Peter H. Zwart, David Baker*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review


    In nature, structural specificity in DNA and proteins is encoded differently: In DNA, specificity arises from modular hydrogen bonds in the core of the double helix, whereas in proteins, specificity arises largely from buried hydrophobic packing complemented by irregular peripheral polar interactions. Here, we describe a general approach for designing a wide range of protein homo-oligomers with specificity determined by modular arrays of central hydrogen-bond networks.We use the approach to design dimers, trimers, and tetramers consisting of two concentric rings of helices, including previously not seen triangular, square, and supercoiled topologies. X-ray crystallography confirms that the structures overall, and the hydrogen-bond networks in particular, are nearly identical to the design models, and the networks confer interaction specificity in vivo. The ability to design extensive hydrogen-bond networks with atomic accuracy enables the programming of protein interaction specificity for a broad range of synthetic biology applications; more generally, our results demonstrate that, even with the tremendous diversity observed in nature, there are fundamentally new modes of interaction to be discovered in proteins.

    Original languageEnglish
    Pages (from-to)680-687
    Number of pages8
    Issue number6286
    Publication statusPublished - 6 May 2016

    ASJC Scopus subject areas

    • General


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