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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…