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A diffusion model for protein design

A team led by Baker Lab scientists Joseph Watson, David Juergens, Nate Bennett, Brian Trippe, and Jason Yim has created a powerful new way to design proteins by combining structure prediction networks and generative diffusion models. The team demonstrated extremely high computational success and tested hundreds of A.I.-generated proteins in the lab, finding that many …

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To improve a cytokine mimic, cut it in half

This week we reported in Nature Biotechnology the design of a conditionally active mimetic of IL-2 that reduces the toxicity of systemic cytokine therapy. This work builds on our prior efforts to create functional interleukin mimics with reduced toxicity. We first described Neoleukin-2/15 (Neo-2/15) in 2019. This compact protein reproduces the immunostimulatory function of IL-2 …

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Machine learning tools can now create new proteins in seconds

ProteinMPNN excels at creating new proteins

Over the past two years, machine learning has revolutionized protein structure prediction. Now, three papers in Science describe a similar revolution in protein design. In the new papers, we show that machine learning can be used to create proteins much more accurately and quickly than previously possible. This could lead to many new vaccines, treatments, …

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Design of permeable peptides leads to new spinout (Vilya)

Researchers at the Institute for Protein Design have discovered how to create peptides that slip through membranes and enter cells. This drug design breakthrough may lead to new medications for a wide variety of health disorders, including cancer, infection, and inflammation. This research appears in the journal Cell [PDF]. Gaurav Bhardwaj, Adam Moyer, Naozumi Hiranuma, …

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Training A.I. to generate medicines and vaccines

Today we report in Science [PDF] the development of artificial intelligence software that can create proteins that may be useful as vaccines, cancer treatments, or even tools for pulling carbon pollution out of the air. This project was led by Jue Wang, Doug Tischer, and Joseph L. Watson, who are postdoctoral scholars at UW Medicine, as well as Sidney Lisanza and David Juergens, …

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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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