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Introducing LOCKR: a bioactive protein switch

Today we report in Nature the design and initial applications of the first completely artificial protein switch that can work inside living cells to modify—or even commandeer—the cell’s complex internal circuitry. The switch is dubbed LOCKR, short for Latching, Orthogonal Cage/Key pRotein. “In the same way that integrated circuits enabled the explosion of the computer …

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Coevolution at the proteome scale

Today we report in Science the identification of hundreds of previously uncharacterized protein–protein interactions in E. coli and the pathogenic bacterium M. tuberculosis. These include both previously unknown protein complexes and previously uncharacterized components of known complexes. This research was led by postdoctoral fellow Qian Cong and included former Baker lab graduate student Sergey Ovchinnikov, now a …

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Protein arrays on mineral surfaces

Today we report the design of synthetic protein arrays that assemble on the surface of mica, a common and exceptionally smooth crystalline mineral. This work, which was performed in collaboration with the De Yoreo lab at PNNL, provides a foundation for understanding how protein-crystal interactions can be systematically programmed.   Designed proteins (orange) form a honeycomb-like …

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Protein design by citizen scientists

Citizen scientists can now use Foldit to successfully design synthetic proteins. The initial results of this unique collaboration appear today in Nature. Brian Koepnick, a recent PhD graduate in the Baker lab, led a team that worked on Foldit behind the scenes, introducing new features into the game that they believed would help players home in …

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Designed ligands tune cytokine signaling

Today we share some exciting collaborative results of our efforts to design rigid and tunable receptor dimerizers! The first authors of this report are Kritika Mohan and George Ueda. From Science: Exploring a range of signaling Cytokines are small proteins that bind to the extracellular domains of transmembrane receptors to activate signaling pathways inside the cell. They often …

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Tunable pH-dependent assemblies

Natural proteins often shift their shapes in precise ways in order to function. Achieving similar molecular rearrangements by design, however, has been a long-standing challenge. Today, a team of researchers lead by scientists at the IPD report in Science the rational design of synthetic proteins that move in response to their environment in predictable and tunable …

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De novo 2D arrays

This week we report in JACS a general approach for designing self-assembling 2D protein arrays. This project was led by Zibo Chen, a recent Baker lab graduate student, and featured collaborators from the, DiMaio, De Yoreo and Kollman labs at UW. Abstract: Modular self-assembly of biomolecules in two dimensions (2D) is straightforward with DNA but has been …

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Potent anti-cancer proteins with fewer side effects

Today we report in Nature the first de novo designed proteins with anti-cancer activity. These compact molecules were designed to stimulate the same receptors as IL-2, a powerful immunotherapeutic drug, while avoiding unwanted off-target receptor interactions. We believe this is just the first of many computer-generated cancer drugs with enhanced specificity and potency. “People have …

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New designer proteins mimic DNA

To close out the year, we published a new report describing the creation of proteins that mimic DNA. We believe this breakthrough will aid the creation of bioactive nanomachines. DNA is a widely used building material at the nanoscale because it is simple and predictable: A pairs with T and C pairs with G. Because …

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Dynamic filaments from scratch

Built to be reversible There has been some success in designing stable peptide filaments; however, mimicking the reversible assembly of many natural protein filaments is challenging. Dynamic filaments usually comprise independently folded and asymmetric proteins and using such building blocks requires the design of multiple intermonomer interfaces. Shen et al. report the design of self-assembling …

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