Design of ordered two-dimensional arrays mediated by noncovalent protein-protein interfaces

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Science  19 Jun 2015:
Vol. 348, Issue 6241, pp. 1365-1368
DOI: 10.1126/science.aaa9897

Designing proteins to self-assemble

DNA has been used as a nano building material since the 1980s. Protein nanostructures have the potential to give greater geometric control and shape variability. Gonen et al. describe the computational design of proteins that self-assemble into two-dimensional arrays. These programmable protein lattices should enable new approaches in biomolecular structure determination and molecular sensing.

Science, this issue p. 1365


We describe a general approach to designing two-dimensional (2D) protein arrays mediated by noncovalent protein-protein interfaces. Protein homo-oligomers are placed into one of the seventeen 2D layer groups, the degrees of freedom of the lattice are sampled to identify configurations with shape-complementary interacting surfaces, and the interaction energy is minimized using sequence design calculations. We used the method to design proteins that self-assemble into layer groups P 3 2 1, P 4 21 2, and P 6. Projection maps of micrometer-scale arrays, assembled both in vitro and in vivo, are consistent with the design models and display the target layer group symmetry. Such programmable 2D protein lattices should enable new approaches to structure determination, sensing, and nanomaterial engineering.

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