Incorporating Pre-training Paradigm for Antibody Sequence-Structure Co-design

Abstract

AbstractAntibodies are versatile proteins that can bind to pathogens and provide effective protection for human body. Recently, deep learning-based computational antibody design has attracted popular attention since it automatically mines the antibody patterns from data that could be complementary to human experiences. However, the computational methods heavily rely on the high-quality antibody structure data, which is quite limited. Besides, the complementarity-determining region (CDR), which is the key component of an antibody that determines the specificity and binding affinity, is highly variable and hard to predict. Therefore, data limitation issue further raises the difficulty of CDR generation for antibodies. Fortunately, there exists a large amount of sequence data of antibodies that can help model the CDR and alleviate the reliance on structured data. By witnessing the success of pre-training models for protein modeling, in this paper, we develop an antibody pre-trained language model and incorporate it into the (antigen-specific) antibody design model in a systemic way. Specifically, we first pre-train an antibody language model based on the sequence data, then propose a one-shot way for sequence and structure generation of CDR to avoid the heavy cost and error propagation from an autoregressive manner, and finally leverage the pre-trained antibody model for the antigen-specific antibody generation model with some carefully designed modules. Through various experiments, we show that our method achieves superior performance over previous baselines on different tasks, such as sequence and structure generation, antigen-binding CDR-H3 design.