AAMAS Conference 2026 Conference Paper
Combinatorial Optimization of Antibody Libraries via Constrained Integer Programming
- Conor F. Hayes
- Andre R Goncalves
- Steven Magana-Zook
- Jacob Pettit
- Ahmet Can Solak
- Daniel Faissol
- Mikel Landajuela
Designing effective antibody libraries is a challenging combinatorial search problem in computational biology. We propose ProtLib- Designer (PLD), a constrained integer linear programming (ILP) method that generates libraries while explicitly controlling library size and diversity. PLD uses in silico deep mutational scanning scores from protein language models and antibody inverse-folding models to guide optimization in a cold-start setting, without requiring target-specific experimental data. Across three antibody– antigensystems(Trastuzumab/HER2, D44. 1/HEL, andSpesolimab/ IL36R), PLDproduceslibrariesthatimprovepredictedbinding-related objectiveswhileenforcinguser-specifieddiversityconstraints. Code is available at github. com/LLNL/protlib-designer.