Summary
The Boltz-2 affinity module for small molecule-protein affinity prediction cannot be effectively repurposed for protein-protein interaction affinity prediction (1). They found that it underperformed fine-tuning from ESM embeddings. However, appending Boltz features to ESM features improves affinity prediction.
1.
King J, Cornwall L, Nica AC, Day J, Sim A, Dalchau N, et al. On fine-tuning Boltz-2 for protein-protein affinity prediction. 2025; Available from: https://arxiv.org/abs/2512.06592