Constraint-Aware Optimization for Robust Protein Stability Prediction

Constraint-Aware Optimization for Robust Protein Stability Prediction

Announce Type: new Abstract: Multimodal $\Delta\Delta G$ predictors integrating protein language models with inverse-folding representations achieve strong in-distribution accuracy on the Megascale dataset but exhibit limited robustness on out-of-distribution (OOD) proteins, persistent forward-reverse bias on paired-mutation benchmarks, and under-representation of rare stabilizing mutations. Existing approaches address these limitations primarily through additional architectural components,...