A5056687229- Protein Structure and Dynamics
- Enzyme Structure and Function
- Hemoglobin structure and function
- Biochemical and Molecular Research
- Advanced Fluorescence Microscopy Techniques
- Biochemical and Structural Characterization
- Advanced Electron Microscopy Techniques and Applications
- Photosynthetic Processes and Mechanisms
- RNA and protein synthesis mechanisms
- Venomous Animal Envenomation and Studies
- Genomics and Phylogenetic Studies
- Metabolomics and Mass Spectrometry Studies
- Mosquito-borne diseases and control
- Supramolecular Self-Assembly in Materials
- Malaria Research and Control
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Machine Learning in Materials Science
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Force Microscopy Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- Genetics, Bioinformatics, and Biomedical Research
- Microbial Metabolic Engineering and Bioproduction
- Lipid Membrane Structure and Behavior
- Photoreceptor and optogenetics research
University of Chicago
2020-2025
University of Washington
2022-2025
Allosteric modulation of protein function, wherein the binding an effector to a triggers conformational changes at distant functional sites, plays central part in control metabolism and cell signalling1–3. There has been considerable interest designing allosteric systems, both gain insight into mechanisms underlying such 'action distance' create synthetic proteins whose functions can be regulated by effectors4–7. However, emulating subtle distributed across many residues, characteristic...
Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually causing severe complications long-lasting disabilities for many more1,2. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including tissue damage3 inhibition nicotinic acetylcholine receptors, resulting in life-threatening neurotoxicity4. At present, the only available treatments snakebites consist polyclonal...
In nature, proteins that switch between two conformations in response to environmental stimuli structurally transduce biochemical information a manner analogous how transistors control flow computing devices. Designing with distinct but fully structured is challenge for protein design as it requires sculpting an energy landscape minima. Here we describe the of “hinge” populate one designed state absence ligand and second presence ligand. X-ray crystallography, electron microscopy, double...
We describe an approach for designing high-affinity small molecule–binding proteins poised downstream sensing. use deep learning–generated pseudocycles with repeating structural units surrounding central binding pockets widely varying shapes that depend on the geometry and number of repeat units. dock molecules interest into most shape complementary these pseudocycles, design interaction surfaces high affinity, experimentally screen to identify designs highest affinity. obtain binders four...
Many proteins form paralogous multimers-molecular complexes in which evolutionarily related are arranged into specific quaternary structures. Little is known about the mechanisms by they acquired their stoichiometry (the number of total subunits complex) and heterospecificity preference for paralogs rather than other copies same protein). Here, we use ancestral protein reconstruction biochemical experiments to study historical increases specificity during evolution vertebrate hemoglobin...
Membraneless organelles, or biomolecular condensates, enable cells to compartmentalize material and processes into unique biochemical environments. While specific, attractive molecular interactions are known stabilize repulsive interactions, the balance between these opposing forces, largely unexplored. Here, we demonstrate that electrostatic regulate condensate stability, internal mobility, interfaces, selective partitioning of molecules both in vitro cells. We find signaling ions, such as...
Abstract G protein-coupled receptors (GPCRs) play key roles in physiology and are central targets for drug discovery development, yet the design of protein agonists antagonists has been challenging as GPCRs integral membrane proteins conformationally dynamic. Here we describe computational de novo methods a high throughput “receptor diversion” microscopy based screen generating GPCR binding miniproteins with affinity, potency selectivity, use these to generate MRGPRX1 CXCR4, GLP1R, GIPR,...
Abstract A general method for designing proteins to bind and sense any small molecule of interest would be widely useful. Due the number atoms interact with, binding molecules with high affinity requires highly shape complementary pockets, transducing events into signals is challenging. Here we describe an integrated deep learning energy based approach complementarity binders that are poised downstream sensing applications. We employ generated psuedocycles repeating structural units...
<title>Abstract</title> Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually causing severe complications long-lasting disabilities for many more<sup>1,2</sup>. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including tissue damage<sup>3</sup> inhibition nicotinic acetylcholine receptors (nAChRs) resulting in life-threatening neurotoxicity<sup>4</sup>. Currently, the...
Many enzymes assemble into homomeric protein complexes comprising multiple copies of one protein. Because structural form is usually assumed to follow function in biochemistry, these assemblies are thought evolve because they provide some functional advantage. In many cases, however, no specific advantage known and, quaternary structure varies among orthologs. This has led the proposition that self-assembly may instead vary neutrally within families. The extent such variation been difficult...
Abstract Many enzymes assemble into homomeric protein complexes comprising multiple copies of one protein. Because structural form is usually assumed to follow function in biochemistry, these assemblies are thought evolve because they provide some functional advantage. In many cases, however, no specific advantage known and, quaternary structure varies among orthologs. This has led the proposition that self-assembly may instead vary neutrally within families. The extent such variation been...
Allosteric modulation of protein function, wherein the binding an effector to a triggers conformational changes at distant functional sites, plays central role in control metabolism and cell signaling 1–3 . There has been considerable interest designing allosteric systems, both gain insight into mechanisms underlying such “action distance” create synthetic proteins whose functions can be regulated by effectors 4–7 However, emulating subtle distributed across many residues, characteristic...
Abstract Proteins that switch between two structural states as a function of environmental stimuli are widespread in nature. These proteins structurally transduce biochemical information manner analogous to how transistors control flow computing devices. Engineering challenges ranging from biological devices molecular motors require such two-state switches, but designing these is an unsolved problem it requires sculpting energy landscape with low-energy distinct conformations can be...
Many proteins form paralogous multimers - molecular complexes in which evolutionarily related are arranged into specific quaternary structures. Little is known about the mechanisms by they acquired their stoichiometry (the number of total subunits complex) and heterospecificity preference for paralogs rather than other copies same protein). Here we use ancestral protein reconstruction biochemical experiments to study historical increases specificity during evolution vertebrate hemoglobin (Hb), a α