A5050658461- RNA and protein synthesis mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Advanced Fluorescence Microscopy Techniques
- Protein Structure and Dynamics
- Photoreceptor and optogenetics research
- Orbital Angular Momentum in Optics
- Advanced Electron Microscopy Techniques and Applications
- Force Microscopy Techniques and Applications
- Enzyme Structure and Function
- Bacteriophages and microbial interactions
- Chemical Synthesis and Analysis
- Protein purification and stability
- Genomics and Phylogenetic Studies
- Mycobacterium research and diagnosis
- Cytomegalovirus and herpesvirus research
- Molecular Junctions and Nanostructures
- Lipid Membrane Structure and Behavior
- CRISPR and Genetic Engineering
- Photosynthetic Processes and Mechanisms
- Machine Learning in Bioinformatics
- Microbial Metabolic Engineering and Bioproduction
University of Washington
2022-2024
Seattle University
2023
Intellectual Ventures (United States)
2021
Bellevue Hospital Center
2021
Although deep learning has revolutionized protein structure prediction, almost all experimentally characterized de novo designs have been generated using physically based approaches such as Rosetta. Here, we describe a learning-based sequence design method, ProteinMPNN, that outstanding performance in both silico and experimental tests. On native backbones, ProteinMPNN recovery of 52.4% compared with 32.9% for The amino acid at different positions can be coupled between single or multiple...
Many peptide hormones form an α-helix on binding their receptors
Despite the central role that antibodies play in modern medicine, there is currently no way to rationally design novel bind a specific epitope on target. Instead, antibody discovery involves time-consuming immunization of an animal or library screening approaches. Here we demonstrate fine-tuned RFdiffusion network capable designing de novo variable heavy chains (VHH's) user-specified epitopes. We experimentally confirm binders four disease-relevant epitopes, and cryo-EM structure designed...
Abstract A wooden house frame consists of many different lumber pieces, but because the regularity these building blocks, structure can be designed using straightforward geometrical principles. The design multicomponent protein assemblies, in comparison, has been much more complex, largely owing to irregular shapes structures 1 . Here we describe extendable linear, curved and angled as well inter-block interactions, that conform specified geometric standards; assemblies blocks inherit their...
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...
Bacterial CRISPR systems provide acquired immunity against invading nucleic acids by activating RNA-programmable RNases and DNases. Cas13a Cas12a enzymes bound to RNA (crRNA) recognize specific acid targets, initiating cleavage of the targets as well non-target (trans) acids. Here, we examine kinetics single-turnover target multi-turnover trans-nuclease activities both enzymes. High-turnover, non-specific trans-RNase activity is coupled rapid binding RNA. By contrast, low-turnover relatively...
Abstract While deep learning has revolutionized protein structure prediction, almost all experimentally characterized de novo designs have been generated using physically based approaches such as Rosetta. Here we describe a sequence design method, ProteinMPNN, with outstanding performance in both silico and experimental tests. The amino acid at different positions can be coupled between single or multiple chains, enabling application to wide range of current challenges. On native backbones,...
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...
Abstract Many peptide hormones form an alpha-helix upon binding their receptors 1–4 , and sensitive detection methods for them could contribute to better clinical management. De novo protein design can now generate binders with high affinity specificity structured proteins 5,6 . However, the of interactions between short helical peptides is unmet challenge. Here, we describe parametric generation deep learning-based designing address this We show that RF diffusion generative model, picomolar...
Abstract A wooden house frame consists of many different lumber pieces, but because the regularity these building blocks, structure can be designed using straightforward geometrical principles. The design multicomponent protein assemblies in comparison has been much more complex, largely due to irregular shapes structures 1 . Here we describe extendable linear, curved, and angled as well inter-block interactions that conform specified geometric standards; blocks inherit their extendability...
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...