Predicting antibody-antigen affinity with a dual-level representation model.

Abstract

Protein language models are critical for modeling antibody-antigen interactions, yet sequence-based affinity prediction remains a key challenge, particularly when structural data are scarce. Existing methods often struggle to fully exploit sequence information, limiting their applicability across diverse antibody formats such as single-domain antibodies (sdAbs). We propose dual-level protein representation for affinity prediction (DLP-Affinity), a dual-level deep learning framework for accurate sequence-based affinity prediction. It leverages two complementary modules: residue-to-residue to capture local interface contacts, and global stochastic projection embedding to represent global protein properties. Utilizing a fine-tuned protein language model, our approach achieves state-of-the-art performance on the general AB-Bind dataset (reducing mean absolute error by up to 20.9%) and delivers highly competitive results on the sdAb-DB dataset. This provides a robust tool for sequence-based antibody affinity prediction. The source code and datasets for DLP-Affinity are freely available at https://github.com/Zy-Wang-bit/DLP_Affinity and archived on Zenodo at https://doi.org/10.5281/zenodo.18437656.