Accurate de novo design of hyperstable constrained peptides

Small constrained peptides combine the stability of small molecule drugs with the selectivity and potency of antibody-based therapeutics. However, peptide-based therapeutics have largely remained underexplored due to the limited diversity of naturally occurring peptide scaffolds, and a lack of methods to design them rationally. In an article published in Nature this week, Baker lab scientists …

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The coming of age of de novo protein design


Most protein design efforts to date have focused on reengineering existing proteins found in nature.  By contrast, de novo protein design generates new structures from scratch, with sequences unrelated to naturally occurring proteins.  Before 2011, the only successful de novo designed proteins were Top7 (2003), and an array of coiled coil peptides (helical bundles).  In …

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Accurate design of megadalton-scale two-component icosahedral protein complexes

Nature provides many examples of self- and co-assembling protein-based molecular machines, including icosahedral protein cages that serve as scaffolds, enzymes, and compartments for essential biochemical reactions and icosahedral virus capsids, which encapsidate and protect viral genomes and mediate entry into host cells. Inspired by these natural materials, we report the computational design and experimental characterization …

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Arrivederci, Fabio!

This past Friday we bid a fond farewell to Fabio Parmegianni as he embarked on his next stage of life, or as some call it, the P.B. (Post-Bakerite) era. Though we will miss him, we wish him the best of luck at the University of Bristol in the UK. The lab will undoubtedly be a …

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Design of a hyperstable 60-subunit protein icosahedron


The icosahedron is the largest of the Platonic solids, and icosahedral protein structures are widely used in biological systems for packaging and transport1, 2. There has been considerable interest in repurposing such structures3, 4, 5 for applications ranging from targeted delivery to multivalent immunogen presentation. The ability to design proteins that self-assemble into precisely specified, …

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Undergrads Being Scientists!


On Friday, May 20, 2016, three of our undergrads participated in the 19th annual Undergraduate Research Symposium. Tessa Howard, Kara Lau, and Vanessa Nguyen presented posters on projects/topics stemming from their work done in our labs. We’d like to recognize the excellent job they did on their presentations! Please see below for their titles and …

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De novo design of protein homo-oligomers with modular hydrogen-bond network-mediated specificity


General design principles for protein interaction specificity are challenging to extract. In DNA, specificity arises from a limited set of hydrogen-bonding interactions in the core of the double helix to design and build a wide range of shapes. In proteins, specificity arises largely from buried hydrophobic packing complemented by irregular peripheral polar interactions. Protein-based materials …

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2015 Lab Holiday Party


On Friday the 18th we had our lab Holiday party! It was supposed to be ugly sweater attire, but only a few of us came dressed appropriately. Fortunately, more people were proactive when participating in the potluck aspect! We had homemade goodies galore, including a creme caramel that had rave reviews, many delicious cookies, an …

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