Antibody-Antigen Docking and Design via Hierarchical Structure Refinement
Proceedings of the 39th International Conference on Machine Learning, PMLR 162:10217-10227, 2022.
Computational antibody design seeks to automatically create an antibody that binds to an antigen. The binding affinity is governed by the 3D binding interface where antibody residues (paratope) closely interact with antigen residues (epitope). Thus, the key question of antibody design is how to predict the 3D paratope-epitope complex (i.e., docking) for paratope generation. In this paper, we propose a new model called Hierarchical Structure Refinement Network (HSRN) for paratope docking and design. During docking, HSRN employs a hierarchical message passing network to predict atomic forces and use them to refine a binding complex in an iterative, equivariant manner. During generation, its autoregressive decoder progressively docks generated paratopes and builds a geometric representation of the binding interface to guide the next residue choice. Our results show that HSRN significantly outperforms prior state-of-the-art on paratope docking and design benchmarks.