AlphaSeq

The highest-throughput and most quantitative approach for measuring protein-protein binding.
Unique Platform Technology

We use synthetic biology to generate high quality protein interaction data at scale.

Hugely Multiplexed

Characterize whole protein-protein interaction networks with millions of interactions

Highly Quantitative

Measure interaction strengths with physiological relevance, spanning picomolar to micromolar affinities

Widely Versatile

Antibody discovery, molecular glue target discovery, orthogonal protein interaction engineering, and more
THE PROCESS

How AlphaSeq Works

  • BUILD

    Two 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.
  • MIX

    The libraries are mixed and incubated in a shaking liquid culture, allowing A and Alpha cells to collide.
  • BIND

    As 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.
  • FUSE

    Bound 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.
  • MEASURE

    Paired A/Alpha barcodes are read and counted with next-generation sequencing. Stronger protein-protein interactions result in a greater frequency of observed barcode pairs.
  • COMPUTE

    Protein-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.
WIDELY VERSATILE

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
 + OPTIMIZATION

    Widen 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 DISCOVERY

    Expand 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 INTERFACES

    Reliably 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 MODELS

    AlphaSeq 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

Recent publications and further research, aided by A-Alpha Bio technology.
To partner with A-Alpha Bio or learn more about how we help you measure protein-protein interactions at scale, please get in touch.
Contact Us