David Baker
YOU?
Author Swipe
View article: Accurate single-domain scaffolding of three nonoverlapping protein epitopes using deep learning
Accurate single-domain scaffolding of three nonoverlapping protein epitopes using deep learning Open
De novo protein design has seen major success in scaffolding single functional motifs; however, in nature, most proteins present multiple functional sites. Here, we describe an approach to simultaneously scaffold multiple functional sites …
View article: Inhibition of ice recrystallization with designed twistless helical repeat proteins
Inhibition of ice recrystallization with designed twistless helical repeat proteins Open
Given the repetitive structure of crystalline ice, it is unsurprising that highly active ice-binding proteins (IBPs), often with beta-roll structures, also have repeating motifs. Here, we introduce a de novo designed family of ice-binding …
View article: Computational design of cysteine proteases
Computational design of cysteine proteases Open
Despite advances in de novo enzyme design, success has been largely limited to low energy barrier model reactions. Amide bonds such as those linking amino acids along the peptide backbone are stable for hundreds of years in neutral aqueous…
View article: Computational design of metalloproteases
Computational design of metalloproteases Open
Although significant progress has been made in creating de novo metalloenzymes that hydrolyze activated esters 1,2 , the energetically demanding cleavage of amide bonds has remained a major challenge for enzyme design: amide bonds are sign…
View article: The Anisotropic Adsorption of De Novo Allosteric Two‐Component Protein Fibers on Mica Surfaces
The Anisotropic Adsorption of De Novo Allosteric Two‐Component Protein Fibers on Mica Surfaces Open
Protein adsorption at solid–liquid interfaces underlies many biomedical and materials applications, yet the mechanisms governing adsorption of proteins and their assemblies remain poorly understood. Here we investigate de novo–designed pro…
View article: Precise mass and radius determination for two new and one known Neptune-sized planets around G Dwarf hosts
Precise mass and radius determination for two new and one known Neptune-sized planets around G Dwarf hosts Open
As part of the KESPRINT collaboration, we present the discovery and characterization of three exoplanets in the sub-Neptune to super-Neptune regime, spanning key regions of the exo-Neptunian landscape. TOI-1472 c and TOI-1648 b are newly d…
View article: Modeling protein–small molecule conformational ensembles with PLACER
Modeling protein–small molecule conformational ensembles with PLACER Open
Modeling the conformational heterogeneity of protein–small molecule interactions is important for understanding natural systems and evaluating designed systems but remains an outstanding challenge. We reasoned that while residue-level desc…
De novo design and evolution of an artificial metathase for cytoplasmic olefin metathesis Open
Artificial metalloenzymes present a promising avenue for abiotic catalysis within living systems. However, their in vivo application is currently limited by critical challenges, particularly in selecting suitable protein scaffolds capable …
View article: EXTH-87. Bifunctional Phagocytic Synapse Enhancers for Cancer Immunotherapy
EXTH-87. Bifunctional Phagocytic Synapse Enhancers for Cancer Immunotherapy Open
Immunotherapy profoundly impacted cancer treatments by harnessing the patient’s immune system. Phagocytosis, the process whereby immune cells engulf and destroy foreign particles or cells, plays a critical role in tumour cell clearance. He…
View article: AI-based HIV-1 Env designs devoid of gp41 mimic native gp120 pre-fusion Env 9395
AI-based HIV-1 Env designs devoid of gp41 mimic native gp120 pre-fusion Env 9395 Open
Description Viral fusion glycoproteins, such as HIV-1 Env, a trimer of gp120 and gp41 heterodimers, are key targets for neutralizing antibodies but are inherently metastable due to conformational changes required for function. Stabilizing …
An IL-21-derived neokine with enhanced anti-tumor efficacy 2594 Open
Description IL-21 is a pleiotropic common-gamma-chain cytokine with diverse actions on immune cells. IL-21 promotes cytotoxicity of CD8+ T cells and NK cells and has been evaluated as a cancer therapy in phase I and II clinical trials. Alt…
View article: De Novo Design of High‐Affinity Miniprotein Binders Targeting <i>Francisella Tularensis</i> Virulence Factor
De Novo Design of High‐Affinity Miniprotein Binders Targeting <i>Francisella Tularensis</i> Virulence Factor Open
Francisella tularensis poses considerable public health risk due to its high infectivity and potential for bioterrorism. Francisella‐like lipoprotein (Flpp3), a key virulence factor unique to Francisella, plays critical roles in infection …
View article: De Novo Design of High‐Affinity Miniprotein Binders Targeting <i>Francisella Tularensis</i> Virulence Factor
De Novo Design of High‐Affinity Miniprotein Binders Targeting <i>Francisella Tularensis</i> Virulence Factor Open
Francisella tularensis poses considerable public health risk due to its high infectivity and potential for bioterrorism. Francisella‐like lipoprotein (Flpp3), a key virulence factor unique to Francisella, plays critical roles in infection …
View article: Tuning insulin receptor signaling using de novo-designed agonists
Tuning insulin receptor signaling using de novo-designed agonists Open
Insulin binding induces conformational changes in the insulin receptor (IR) that activate the intracellular kinase domain and the protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) pathways, regulating metabolism and prolif…
View article: Direct cell reprogramming by a designed agonist inducing HER2-FGFR proximity
Direct cell reprogramming by a designed agonist inducing HER2-FGFR proximity Open
Growth factor induced receptor dimerization and activation of downstream pathways can modulate cell fate decisions. Here, we investigate the potential of de novo designed synthetic ligands, termed Novokines, to reprogram cell identity by i…
View article: High-Throughput De Novo Protein Design Yields Novel Immunomodulatory Agonists
High-Throughput De Novo Protein Design Yields Novel Immunomodulatory Agonists Open
Cytokines regulate cell behavior by bringing together specific receptor subunits to trigger downstream signaling. Designed molecules that bring together non-natural receptor pairs could have novel signaling responses and cell specificities…
View article: Geometric Tuning of Cytokine Receptor Association Modulates Synthetic Agonist Signaling
Geometric Tuning of Cytokine Receptor Association Modulates Synthetic Agonist Signaling Open
Cytokines signal by bringing receptor subunits together, but the role of receptor geometry in shaping signaling remains unclear because natural ligands enforce fixed assemblies. Here, we present a de novo protein design platform that rigid…
Multiplex design and discovery of proximity handles for programmable proteome editing Open
Although we now have a rich toolset for genome editing, an equivalent framework for manipulating the proteome with a comparable flexibility and specificity remains elusive. A promising strategy for “proteome editing” is to use bifunctional…
View article: RNA sequence design and protein–DNA specificity prediction with NA-MPNN
RNA sequence design and protein–DNA specificity prediction with NA-MPNN Open
RNA sequence design and protein–DNA binding specificity prediction can both be framed as nucleic acid inverse-folding problems: finding the most likely nucleic acid sequences given a fixed three-dimensional structure of a nucleic acid or n…
View article: De novo design of RNA and nucleoprotein complexes
De novo design of RNA and nucleoprotein complexes Open
Nucleic acids fold into sequence-dependent tertiary structures and carry out diverse biological functions, much like proteins. However, while considerable advances have been made in the de novo design of protein structure and function, the…
View article: De-novo design of a random protein walker
De-novo design of a random protein walker Open
Molecular machines hold great potential. Design of static monomeric and oligomeric protein structures has advanced tremendously, but few dynamic protein systems have been designed. Here we present the design and characterization of a rando…
View article: <i>De novo</i> design of phospho-tyrosine peptide binders
<i>De novo</i> design of phospho-tyrosine peptide binders Open
Phosphorylation on tyrosine is a key step in many signaling pathways. Despite recent progress in de novo design of protein binders, there are no current methods for designing binders that recognize phosphorylated proteins and peptides; thi…
Computational design of pH-sensitive binders Open
pH gradients are central to physiology, from vesicle acidification to the acidic tumor microenvironment. While therapeutics have been developed to exploit these pH changes to modulate activity across different physiological environments, c…
View article: Design of a potent interleukin-21 mimic for cancer immunotherapy
Design of a potent interleukin-21 mimic for cancer immunotherapy Open
Long-standing goals of cancer immunotherapy are to activate cytotoxic antitumor T cells across a range of affinities for tumor antigens while suppressing regulatory T cells. Computational protein design has enabled the precise tailoring of…
Design of facilitated dissociation enables timing of cytokine signalling Open
Protein design has focused on the design of ground states, ensuring that they are sufficiently low energy to be highly populated 1 . Designing the kinetics and dynamics of a system requires, in addition, the design of excited states that a…
View article: De novo design of potent inhibitors of clostridial family toxins
De novo design of potent inhibitors of clostridial family toxins Open
Clostridioides difficile remains a leading cause of hospital-acquired infections, with its primary virulence factor, toxin B (TcdB), responsible for severe colitis and recurrent disease. The closely related toxin, TcsL, from Paeniclostridi…