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

By S. Gonen, Frank DiMaio, Tamir Gonen, David Baker. 2015

222 citations recorded by the source corpus.

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 A computational approach allows the design of proteins that self-assemble into two-dimensional lattices. 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.

Subfields: Ecology, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Ecology

In Molecular Biology

Citations in the corpus

The coming of age of de novo protein design (2016, background): “78 and J. Fallas and G. Ueda, personal communication), tetrahedra 79,80 , octahedra 79 and open two-dimensional assemblies 81 (Fig.”
Reconfigurable asymmetric protein assemblies through implicit negative design (2021, unknown): “Previous design efforts have generated cyclic oligomeric and higher-order symmetric nanostructures such as icosahedral nano-cages with as many as 120 subunits and two-dimensional (2D) – layers with many thousands of regularly arrayed components ( 4 – 8 ).”
De novo protein design, a retrospective (2020, methodology): “More recently, similar methods have been used by Baker et al., to design a number of different lattices, in this case using natural proteins with cyclic symmetry as the basic building blocks (Gonen et al., 2015).”
Designing Peptides on a Quantum Computer (2019, methodology): “Rosetta has been used to design new protein topologies ( 2 , 3 ) , large macromolecular assemblies ( 4 – 7 ) , proteins with the ability to bind to toxic small molecules ( 8 , 9 ) or to other proteins of therapeutic interest ( 10 , 11 ) , and enzymes able to catalyze reactions that no known natural…”
Recent advances in de novo protein design: Principles, methods, and applications (2021, methodology): “Exciting recently designed functions include inhibitors of viral infections (3, 4), immune system modulators (5, 6), self-assembling biomaterials (7 – 9), sense-and-respond signaling systems (10 – 13), and protein logic gates (14, 15).”