Category: Publication

New protein assemblies with hundreds of subunits dwarf common viral capsids.

Generative AI based on RFdiffusion designs cyclic peptides with atomic accuracy.

“When we started with this idea a few years ago, many people thought it was impossible.”

This advance could allow scientists to create cheaper alternatives to antibodies for disease detection and treatment. This week we report in Nature an AI-enabled advance in biotechnology with implications for drug development, disease detection, and environmental monitoring. Using a combination of traditional and deep learning based molecular design approaches, we’ve created proteins that bind with…

Our research shows that custom proteins can drive the growth of limestone-like minerals, a breakthrough that may one day help remove excess carbon from the environment.

Recent deep-learning breakthroughs allow us to look beyond just amino acids, expanding the types of proteins that can be modeled and designed using RoseTTAFold and RFdiffusion.

Today we report in Nature the design of proteins that recognize and bind to the so-called “intrinsically disordered regions” of proteins and peptides. The body produces such disordered molecules naturally, but many have been linked to health disorders, including myeloma and other cancers. “Disordered proteins play important roles in biology. By designing new proteins that…

The de novo design of small proteins with beta-barrel topologies has been a challenge for computational design due to the complexity inherent in these folds. In a new study appearing in PNAS, a team led by Baker Lab research scientist David E. Kim describes the successful design and characterization of four different classes of small…

King Lab postdoctoral scholars John Wang and Alena Khmelinskaia have developed a new tool for identifying and removing hidden transmembrane sequences that hinder protein secretion.

Under ideal conditions, cryo-electron microscopy can be used to determine protein structures at near-atomic resolution. But conditions are not always perfect. To help researchers make use of medium-resolution cryo-electron density maps, scientists in the DiMaio Lab have developed EMERALD, which is a new software tool that can accurately and automatically produce deposition-ready small molecule models…

Today we report in Nature the computational design of highly efficient enzymes unlike any found in nature. Laboratory testing confirms that the new light-emitting enzymes can recognize specific chemical substrates and catalyze the emission of photons very efficiently.

Update (July 2023): Our manuscript on the development of RFdiffusion has been published in Nature. A team led by scientists from the Baker Lab has created a powerful new way of designing proteins that combines structure prediction networks and generative diffusion models. The team demonstrated extremely high computational success using the new method and experimentally…

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]. “This new ability to design membrane-permeable…

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,…

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…

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 treatments for…

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…

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…

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 that are common to all animals, plants, and fungi. This open-access work appears in Science.…

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…

IPD researchers together with collaborators at the National Institutes of Health have developed experimental flu shots that protect animals from a wide variety of seasonal and pandemic influenza strains. The lead vaccine candidate has entered human clinical testing at the NIH. If it proves safe and effective, these next-generation influenza vaccines may replace current seasonal…

Scientists at the IPD and Ovchinnikov lab at Harvard have applied deep learning to the challenge of protein design, yielding a new way to quickly create protein sequences that fold up as desired. This breakthrough has broad implications for the development of protein-based medicines and vaccines. Computational protein design has primarily focused on finding amino…

Biochemists have created barrel-shaped proteins that embed into lipid membranes, expanding the bioengineering toolkit. In a milestone for biomolecular design, a team of scientists has succeeded in creating new proteins that adopt one of the most complex folds known to molecular biology. These designer proteins were shown in the lab to spontaneously fold into their…

Today we report the design of a new class of protein material that interacts with living cells without being absorbed by them. These large, flat arrays built from multiple protein parts can influence cell signaling by clustering and anchoring cell surface receptors. This breakthrough could have far-reaching implications for stem cell research and enable the…

In a new paper [PDF] appearing in Science, a team of IPD researchers together with colleagues at UW Medicine and Fred Hutchinson Cancer Research Center demonstrate a new way to precisely target cells — including those that look almost exactly like their neighbors. They designed nanoscale devices made of synthetic proteins that target a therapeutic agent only to cells with…

The same basic tools that allow computers to function are now being used to control life at the molecular level, with implications for future medicines and synthetic biology.  Together with collaborators, we have created artificial proteins that function as molecular logic gates. These tools, like their electronic counterparts, can be used to program the behavior…

Today we report the design of protein sequences that adopt more than one well-folded structure, reminiscent of viral fusion proteins. This research moves us closer to creating artificial protein systems with reliable moving parts. In nature, many proteins change shape in response to their environment. This plasticity is often linked to biological function. While computational…

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 chip industry, these versatile and dynamic…

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 John Harvard Distinguished Science…

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. Our goal was to engineer artificial proteins to self-assemble on…

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 on…

Today the Baker lab shares some exciting collaborative results of their efforts to design rigid and tunable receptor dimerizers. The first authors of this report are Kritika Mohan, Stanford, and George Ueda, IPD. From Science: Exploring a range of signaling Cytokines are small proteins that bind to the extracellular domains of transmembrane receptors to activate signaling pathways…

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…

This week we report in NSMB a combined computational design and experimental selection approach for creating proteins that bind selectively to closely related receptor subtypes. This project was led by Luke Dang, a former Baker lab graduate student, and Yi Miao, a postdoctoral researcher in Christopher Garcia’s lab at Stanford. Abstract: To discriminate between closely related members of…

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…

Today we report in Cell our first computer-designed nanoparticle vaccine targeting respiratory syncytial virus, the primary cause of pneumonia in young children and the leading cause of infant mortality worldwide after malaria. Although virtually every child will get infected by RSV before the age of three, an estimated 99 percent of deaths associated with the…

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 tried for 30…

To close out the year, Baker Lab scientists 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…

The basic parts of proteins — helices, strands and loops — can be combined in countless ways. But certain combinations are trickier than others. This week scientists from the IPD, along with collaborators in Brno and Santa Cruz, published the first-ever example of designed non-local beta-strand interactions. Beta-sheet proteins carry out critical functions in biology,…

In the summer of 1961, Osamu Shimomura drove across the country in a cramped station wagon to scoop jellyfish from the docks of Friday Harbor. He wanted to discover what made them glow. It took Shimomura and other biochemists more 30 years to find a full answer. By then, recombinant DNA technology allowed researchers to…

Today at 11am, the paper titled “A Computationally Designed Hemagglutinin Stem-Binding Protein Provides In Vivo Protection from Influenza Independent of a Host Immune Response” was published to the PLOS Pathogen website. This paper was contributed to by several IPD members, including Aaron Chevalier, Jorgen Nelson, Lance Stewart, Lauren Carter, and David Baker. The research was performed…

[envira-gallery id=”3246″] Custom design with atomic level accuracy enables researchers to craft a whole new world of proteins Naturally occurring proteins are the nanoscale machines that carry out essentially all of the critical functions in living things. While it has been known for over 40 years that the sequence of amino acids completely determines the…

In the early 1990s, researchers in the field of protein structure prediction were challenged by the problem of how to impartially judge the accuracy of prediction algorithms.  This realization led the protein structure prediction the community to start the Critical Assessment of protein Structure Prediction (CASP), a community-wide, worldwide experiment for protein structure prediction taking…