A5037232302- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Enzyme Structure and Function
- Transgenic Plants and Applications
- Genomics and Phylogenetic Studies
- Nanopore and Nanochannel Transport Studies
- CRISPR and Genetic Engineering
- Viral Infectious Diseases and Gene Expression in Insects
- Monoclonal and Polyclonal Antibodies Research
- Mass Spectrometry Techniques and Applications
- Modular Robots and Swarm Intelligence
- Machine Learning in Materials Science
- Lipid Membrane Structure and Behavior
- Ubiquitin and proteasome pathways
- Advanced NMR Techniques and Applications
- Computational Drug Discovery Methods
- Software Engineering Research
- Robotic Path Planning Algorithms
- Genetics, Bioinformatics, and Biomedical Research
- Bacterial Genetics and Biotechnology
- Chemical Synthesis and Analysis
- Biochemical and Structural Characterization
- Advanced Electron Microscopy Techniques and Applications
- Protein purification and stability
University of Washington
2015-2024
Align Technology (United States)
2024
The Align Foundation
2024
Seattle University
2021-2023
University of Massachusetts Amherst
2003-2011
Abstract General approaches for designing sequence-specific peptide-binding proteins would have wide utility in proteomics and synthetic biology. However, is challenging, as most peptides do not defined structures isolation, hydrogen bonds must be made to the buried polar groups peptide backbone 1–3 . Here, inspired by natural re-engineered protein–peptide systems 4–11 , we set out design of repeating units that bind with sequences, a one-to-one correspondence between repeat protein those...
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...
A systematic and robust approach to generating complex protein nanomaterials would have broad utility. We develop a hierarchical designing multi-component assemblies from two classes of modular building blocks: designed helical repeat proteins (DHRs) bundle oligomers (HBs). first rigidly fuse DHRs HBs generate large library oligomeric blocks. then with cyclic, dihedral, point group symmetries these blocks using architecture guided rigid fusion new software named WORMS. X-ray crystallography...
Abstract In natural proteins, structured loops have central roles in molecular recognition, signal transduction and enzyme catalysis. However, because of the intrinsic flexibility irregularity loop regions, organizing multiple at protein functional sites has been very difficult to achieve by de novo design. Here we describe a solution this problem that designs tandem repeat proteins with (9–14 residues) buttressed extensive hydrogen bonding interactions. Experimental characterization shows...
Molecular systems with coincident cyclic and superhelical symmetry axes have considerable advantages for materials design as they can be readily lengthened or shortened by changing the length of constituent monomers. Among proteins, alpha-helical coiled coils such symmetric, extendable architectures, but are limited relatively fixed geometry flexibility helical protomers. Here we describe a systematic approach to generating modular rigid repeat protein oligomers C
The ability to precisely design large proteins with diverse shapes would enable applications ranging from the of protein binders that wrap around their target positioning multiple functional sites in specified orientations. We describe a backbone method for generating wide range rigid fusions between helix-containing and use it 75,000 structurally unique junctions monomeric homo-oligomeric de novo designed ankyrin repeat (RPs). Of junction designs were experimentally characterized, 82% have...
Abstract The de novo design of three protein chains that associate to form a heterotrimer (but not any the possible two-chain heterodimers) and can drive assembly higher-order branching structures is an important challenge for design. We designed helical heterotrimers with specificity conferred by buried hydrogen bond networks large aromatic residues enhance shape complementary packing. obtained ten designs which all cooperatively assembled into few or no other species present. Crystal...
Abstract The grand challenge of protein engineering is the development computational models to characterize and generate sequences for arbitrary functions. Progress limited by lack 1) benchmarking opportunities, 2) large function datasets, 3) access experimental characterization. We introduce Protein Engineering Tournament—a fully-remote competition designed foster evaluation approaches in engineering. tournament consists an silico round, predicting biophysical properties from sequences,...
Presents techniques for exploiting redundancy in teams of mobile robots. In particular, we address tasks involving the kinematic coordination several communicating Teams area modeled as highly redundant spatial mechanisms which multi-objective, concurrent controllers are constructed using a generalization null-space control. The goal is to develop methodology robustness and error suppression control theoretic substrate can be used preserve critical properties reactive resulting "safe"...
Abstract The most significant impediment for protein structure prediction is the inadequacy of conformation space search. Conformation too large and energy landscape rugged existing search methods to consistently find near‐optimal minima. To alleviate this problem, we present model‐based search, a novel method. Model‐based uses highly accurate information obtained during build an approximate, partial model landscape. aggregates in as it progresses, turn guide exploration toward regions...
Function follows form in biology, and the binding of small molecules requires proteins with pockets that match shape ligand. For design to symmetric ligands, protein homo-oligomers matching symmetry are advantageous as each subunit can make identical interactions Here, we describe a general approach designing hyperstable C2 diverse size shape. We first designed repeat sample continuum curvatures but have low helical rise, then docked these into homodimers generate an extensive range...
Motivation:De novo protein structure prediction can be formulated as search in a high-dimensional space. One of the most frequently used computational tools to solve such problems is Monte Carlo method. We present novel technique, called model-based search. This method samples space build an approximate model underlying function. incrementally refined areas interest, whereas that are not interest excluded from further exploration. Model-based derives its efficiency fact information obtained...
We describe the identification and characterization of novel homing endonucleases using genome database mining to identify putative target sites, followed by high throughput activity screening in a bacterial selection system. characterized substrate specificity kinetics these monitoring DNA cleavage events with deep sequencing. The endonuclease specificities revealed experiments can be partially recapitulated 3D structure-based computational models. Analysis models together sequence data...
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...
Abstract A goal of de novo protein design is to develop a systematic and robust approach generating complex nanomaterials from stable building blocks. Due their structural regularity simplicity, wide range monomeric repeat proteins oligomeric helical bundle structures have been designed characterized. Here we describe stepwise hierarchical up multi-component symmetric assemblies using these structures. We first connect (DHRs) (HBs) generate large library heterodimeric homooligomeric blocks;...
The grand challenge of protein engineering is the development computational models that can characterize and generate sequences for any arbitrary function. However, progress today limited by lack 1) benchmarks with which to compare techniques, 2) large datasets function, 3) democratized access experimental characterization. Here, we introduce Protein Engineering Tournament, a fully-remote, biennial competition benchmarking methods in engineering. tournament consists two rounds: first silico...
In natural proteins, structured loops play central roles in molecular recognition, signal transduction and enzyme catalysis. However, because of the intrinsic flexibility irregularity loop regions, organizing multiple at protein functional sites has been very difficult to achieve by
Abstract Molecular systems with coincident cyclic and superhelical symmetry axes have considerable advantages for materials design as they can be readily lengthened or shortened by changing the length of constituent monomers. Among proteins, alpha helical coiled coils such symmetric extendable architectures, but are limited relatively fixed geometry flexibility protomers. Here, we describe a systematic approach to generating modular rigid repeat protein oligomers C 2 8 that extended...