AntiBinder: utilizing bidirectional attention and hybrid encoding for precise antibody–antigen interaction prediction

Abstract Antibodies play a key role in medical diagnostics and therapeutics. Accurately predicting antibody–antigen binding is essential for developing effective treatments. Traditional protein–protein interaction prediction methods often fall short because they do not account for the unique structural and dynamic properties of antibodies and antigens. In this study, we present AntiBinder, a novel predictive model specifically designed to address these challenges. AntiBinder integrates the unique structural and sequence characteristics of antibodies and antigens into its framework and employs a bidirectional cross-attention mechanism to automatically learn the intrinsic mechanisms of antigen–antibody binding, eliminating the need for manual feature engineering. Our comprehensive experiments, which include predicting interactions between known antigens and new antibodies, predicting the binding of previously unseen antigens, and predicting cross-species antigen–antibody interactions, demonstrate that AntiBinder outperforms existing state-of-the-art methods. Notably, AntiBinder excels in predicting interactions with unseen antigens and maintains a reasonable level of predictive capability in challenging cross-species prediction tasks. AntiBinder’s ability to model complex antigen–antibody interactions highlights its potential applications in biomedical research and therapeutic development, including the design of vaccines and antibody therapies for rapidly emerging infectious diseases.