How AlphaSeq Works
BUILDTwo yeast surface display libraries are built from synthesized or template DNA. Displayed proteins may include antibodies, cell surface receptors, intracellular proteins, bacterial or viral antigens, peptides, and more.
MIXThe libraries are mixed and incubated in a shaking liquid culture, allowing A and Alpha cells to collide.
BINDAs cells collide, proteins on the cells’ surfaces may lead them to bind, where the probability of binding depends on protein interaction strength. Each surface expressed protein is paired with a unique DNA barcode.
FUSEBound A and Alpha cells fuse, combining DNA barcodes into the same cellular compartment. A recombination event then pairs the barcodes onto the same strand of DNA.
MEASUREPaired A/Alpha barcodes are read and counted with next-generation sequencing. Stronger protein-protein interactions result in a greater frequency of observed barcode pairs.
COMPUTEProtein-protein interaction affinities are estimated using internal controls and DNA barcodes. The resulting protein-protein interaction dataset is processed to generate application-specific insights and data visualizations.
Some of our focus areas are listed below. Please contact us to inquire about these or any other applications of interest.
Protein-protein interactions are central to all of biology and are the key mechanism of action for antibodies, molecular glues, cell therapies, and more. Some of our focus areas are listed below. Please contact us to inquire about these or any other applications of interest.
ANTIBODY DISCOVERY + OPTIMIZATIONWiden the discovery funnel to find the best antibodies. AlphaSeq enables our partners to discover antibodies with rare and desirable properties by determining the affinity, specificity, cross-reactivity, and epitope of thousands of antibodies at a time.
MOLECULAR GLUE TARGET DISCOVERYExpand the potential of targeted protein degradation to more ligases and more targets. AlphaSeq enables our partners to discover weak ligase-substrate interactions and efficiently test their druggability at high throughput.
ENGINEERING ORTHOGONAL INTERFACESReliably engineer orthogonal protein-protein interactions with two-sided mutagenesis. AlphaSeq enables our partners to develop cell therapy platforms, novel antibody formats, synthetic enzyme scaffolds, and more.
MACHINE LEARNING MODELSAlphaSeq protein-protein interaction data is both quantitative and multi-dimensional, making it ideal for training highly predictive machine learning models for complex properties like affinity, specificity, cross-reactivity and epitope.
Publications + Resources
- Learn more2021
Massively Multiplexed Affinity Characterization of Therapeutic Antibodies Against SARS-CoV-2 VariantsEmily Engelhart, Randolph Lopez, Ryan Emerson, Charles Lin, Colleen Shikany, Daniel Guion, Mary Kelley, David Younger
- Lear more2017David Younger, Stephanie Berger, David Baker, and Eric Klavins