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Custom biosensors for detecting coronavirus antibodies in blood

Today we report in Nature Biotechnology the design of custom protein-based biosensors that can detect coronavirus-neutralizing antibodies in blood. This research, which builds on prior sensor design technology in the lab, was led by Baker lab postdoctoral scholars Jason Zhang, PhD, and Hsien-Wei (Andy) Yeh, PhD. From Behind the Paper: [W]e utilized the de novo …

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De novo designed rotary proteins

Today we report in Science the design of rotary devices made from custom proteins. These microscopic “axles” and “rotors” come together to form spinning assemblies, rather than being locked in just one orientation. Such mechanical coupling is a key feature of any machine. The new axle-rotor devices — which are each about a billion times smaller than …

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New COVID-19 nasal spray outperforms current antibody treatments in mice

A new protein-based antiviral nasal spray developed by Baker lab researchers in collaboration with scientists Northwestern University, UW Medicine, and Washington University at St. Louis is being advanced toward Phase I human clinical trials to treat COVID-19. Designed computationally and refined in the laboratory, the new protein therapies thwarted infection by interfering with the virus’ …

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Design of proteins binders from target structure alone

Today we report in Nature a new method for generating protein drugs. Using Rosetta-based design, an international team designed molecules that can target important proteins in the body, such as the insulin receptor, as well as proteins on the surface of viruses. This solves a long-standing challenge in drug development and may lead to new …

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Diverse protein assemblies by (negative) design

A new approach for creating custom protein complexes yields asymmetric assemblies with interchangeable parts. Today we report in Science the design of new protein assemblies made from modular parts. These complexes — which adopt linear, branching, or closed-loop architectures — contain up to six unique proteins, each of which remains folded and soluble in the absence …

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Deep learning dreams up new protein structures

Just as convincing images of cats can be created using artificial intelligence, new proteins can now be made using similar tools. In a new report in Nature, we describe the development of a neural network that “hallucinates” proteins with new, stable structures. “For this project, we made up completely random protein sequences and introduced mutations into …

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Deep learning reveals how proteins interact

A team led by scientsts in the Baker lab has combined recent advances in evolutionary analysis and deep learning to build three-dimensional models of how most proteins in eukaryotes interact. This breakthrough has significant implications for understanding the biochemical processes common to all animals, plants, and fungi. This open-access work appears in Science. “To really …

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Accurate protein structure prediction accessible to all

Today we report the development and initial applications of RoseTTAFold, a software tool that uses deep learning to quickly and accurately predict protein structures based on limited information. Without the aid of such software, it can take years of laboratory work to determine the structure of just one protein. With RoseTTAFold, a protein structure can be …

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Hitching a ride into the brain

In a new paper, we describe a general approach for designing proteins that bind to exposed polar backbone groups at the edge of beta sheets with geometrically matched beta strands. We used this approach to create small proteins that bind to an exposed beta sheet on the human transferrin receptor, which shuttles interacting proteins across …

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Designed proteins assemble antibodies into modular nanocages

This week we report the design of new proteins that cluster antibodies into dense particles, rendering them more effective. In laboratory testing, such clustered antibodies neutralize COVID-19 pseudovirus, enhance cell signaling, and promote the growth of T cells more effectively than do free antibodies. This new method for enhancing antibody potency may eventually be used …

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