Zero-shot antibody design in a 24-well plate @chaidiscovery 1. Researchers have introduced Chai-2, a multimodal generative model that marks a significant leap in de novo antibody and miniprotein design. This platform achieves an impressive 16% hit rate in de novo antibody design, which represents over a 100-fold improvement compared to previous computational methods. 2. Chai-2 also demonstrates a 68% wet-lab success rate in miniprotein design, consistently yielding picomolar binders. This high success rate enables rapid experimental validation and characterization of novel antibodies within two weeks, accelerating the drug discovery timeline. 3. The model was prompted to design up to 20 antibodies or nanobodies for 52 diverse targets, none of which had pre-existing binders in the Protein Data Bank. Remarkably, at least one successful hit was found for 50% of these targets in just a single round of experimental testing, often with strong affinities and favorable drug-like profiles. 4. Chai-2 facilitates a complete workflow from AI design to wet-lab validation in under two weeks, enabling discovery in a single 24-well plate. This drastically reduces experimental timelines from months or years to just weeks, tightening the design-validation feedback loop. 5. A key innovation of Chai-2 is its ability to perform "zero-shot" design, generating candidate binders for any specified binding site with just a few residues and without requiring a known starting binder. It can also generate sequences in various modalities, including scFv antibodies, VHH domains, or minibinders. 6. The platform successfully designed the first computationally designed hit against TNFα, a challenging target previously considered intractable for computational protein design due to its highly flat and polar binding site. 7. The designed antibodies are novel and diverse, confirmed by structural and sequence analysis, and exhibit favorable developability profiles. Chai-2 also allows for the optimization of designs for specific therapeutic requirements, such as species cross-reactivity. 📜Paper: biorxiv.org/content/10.1101/… #AntibodyDesign #ProteinDesign #AIDrugDiscovery #ComputationalBiology #Biologics #Chai2 #DeNovoDesign #DrugDiscovery