AbLIFT

AbLIFT designs multipoint core mutations in antibody variable fragments (Fv) to optimize stability, expressibility, and affinity by targeting the light–heavy chain interface.

Key Features:

• Multipoint Core Mutation Design: Designs mutations within the core of the antibody Fv, specifically at the light–heavy chain interface rather than only on solvent-exposed surfaces.
• Deep Mutational Scanning Integration: Leverages deep mutational scanning data derived from yeast display to identify beneficial substitutions and map mutational tolerance.
• Structural Modeling and Mutational Tolerance Mapping: Uses structural modeling to predict the effects of mutations and to systematically map tolerable multipoint changes.
• Rosetta Design Integration: Integrates the Rosetta software suite to combine affinity-enhancing mutations and predict variant energetics for improved stability and affinity.
• Automated Computational Design: Automates generation and evaluation of multipoint mutation combinations using the above data and modeling components.

Scientific Applications:

• Stability and Affinity Optimization: Improves antibody stability, affinity, and expression yields through designed multipoint core mutations.
• Antibodies against VEGF and QSOX1: Has been applied to optimize antibodies targeting VEGF (Vascular Endothelial Growth Factor) and QSOX1.
• Therapeutic and Diagnostic Antibody Engineering: Accelerates development of high-performance antibodies for therapeutic and diagnostic applications by reducing iterative experimental cycles.

Methodology:

Begins with deep mutational scanning using yeast display to identify candidate mutations, applies structural and computational modeling to predict mutational effects and optimize Fv light–heavy chain contacts, and uses Rosetta design to combine affinity-enhancing mutations.