A5013668335- Monoclonal and Polyclonal Antibodies Research
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Advanced Electron Microscopy Techniques and Applications
- Advanced Proteomics Techniques and Applications
- Glycosylation and Glycoproteins Research
- Microbial Community Ecology and Physiology
- Genomics and Phylogenetic Studies
- Chemical Synthesis and Analysis
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Amino Acid Enzymes and Metabolism
- Force Microscopy Techniques and Applications
- Peptidase Inhibition and Analysis
- SARS-CoV-2 and COVID-19 Research
- Advanced Biosensing Techniques and Applications
- Genetics, Bioinformatics, and Biomedical Research
- Biochemical and Structural Characterization
University of Washington
2014-2021
Seattle University
2021
Integrating form and function for design Antibodies are broadly used in therapies as research tools because they can be generated against a wide range of targets. Efficacy often increased by clustering antibodies multivalent assemblies. Divine et al. designed antibody nanocages from two components: One is an antibody-binding homo-oligomic protein the other itself. Computationally proteins drive assembly architectures, allowing control symmetry valency. The display enhances antibody-dependent...
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...
Significance The de novo design of proteins that bind natural target is useful for a variety biomedical and biotechnological applications. We describe strategy to containing an exposed beta edge strand. use the approach binders human transferrin receptor which shuttles back forth across blood–brain barrier. Such could be delivery therapeutics into brain.
Significance Designed protein assemblies have many applications in medicine and technology. A long-standing design paradigm generates through genetic fusion of homo-oligomers via α-helical linkers. Here, we introduce a rigid strategy that finds greater number solutions reduces formation unintended assembly states, method for doubly anchoring target binding domains the resulting could contribute to cryogenic electron microscopy structure determination small proteins.
d-amino acids are useful building blocks for de novo peptide design and they play a role in aging-related diseases associated with gradual protein racemization. For amino achiral side chains, one should be able to presume that the conformational propensities of l- reflection another due straightforward geometric inversion at Cα atom. However, this presumption does not account directionality backbone dipole inverted have never been definitively confirmed context. Furthermore, there is little...
Abstract Antibodies are widely used in biology and medicine, there has been considerable interest multivalent antibody formats to increase binding avidity enhance signaling pathway agonism. However, currently no general approaches for forming precisely oriented assemblies with controlled valency. We describe the computational design of two-component nanocages that overcome this limitation by uniting form function. One structural component is any or Fc fusion second a designed Fc-binding...
Abstract Protein nanomaterial design is an emerging discipline with applications in medicine and beyond. A longstanding approach uses genetic fusion to join protein homo-oligomer subunits via α-helical linkers form more complex symmetric assemblies, but this method hampered by linker flexibility a dearth of geometric solutions. Here, we describe general computational that performs rigid three-body spacer building blocks generate user-defined architectures, while at the same time...
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;...