Principles for designing proteins with cavities formed by curved β sheets

See allHide authors and affiliations

Science  13 Jan 2017:
Vol. 355, Issue 6321, pp. 201-206
DOI: 10.1126/science.aah7389

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Designing proteins with cavities

In de novo protein design, creating custom-tailored binding sites is a particular challenge because these sites often involve nonideal backbone structures. For example, curved b sheets are a common ligand binding motif. Marcos et al. investigated the principles that drive β-sheet curvature by studying the geometry of β sheets in natural proteins and folding simulations. In a step toward custom design of enzyme catalysts, they used these principles to control β-sheet geometry and design proteins with differently shaped cavities.

Science, this issue p. 201


Active sites and ligand-binding cavities in native proteins are often formed by curved β sheets, and the ability to control β-sheet curvature would allow design of binding proteins with cavities customized to specific ligands. Toward this end, we investigated the mechanisms controlling β-sheet curvature by studying the geometry of β sheets in naturally occurring protein structures and folding simulations. The principles emerging from this analysis were used to design, de novo, a series of proteins with curved β sheets topped with α helices. Nuclear magnetic resonance and crystal structures of the designs closely match the computational models, showing that β-sheet curvature can be controlled with atomic-level accuracy. Our approach enables the design of proteins with cavities and provides a route to custom design ligand-binding and catalytic sites.

View Full Text

Stay Connected to Science