AbDPP: Target‐oriented antibody design with pretraining and prior biological structure knowledge

Abstract Antibodies represent a crucial class of complex protein therapeutics and are essential in the treatment of a wide range of human diseases. Traditional antibody discovery methods, such as hybridoma and phage display technologies, suffer from limitations including inefficiency and a restricted exploration of the immense space of potential antibodies. To overcome these limitations, we propose a novel method for generating antibody sequences using deep learning algorithms called AbDPP (target‐oriented antibody design with pretraining and prior biological knowledge). AbDPP integrates a pretrained model for antibodies with biological region information, enabling the effective use of vast antibody sequence data and intricate biological system understanding to generate sequences. To target specific antigens, AbDPP incorporates an antibody property evaluation model, which is further optimized based on evaluation results to generate more focused sequences. The efficacy of AbDPP was assessed through multiple experiments, evaluating its ability to generate amino acids, improve neutralization and binding, maintain sequence consistency, and improve sequence diversity. Results demonstrated that AbDPP outperformed other methods in terms of the performance and quality of generated sequences, showcasing its potential to enhance antibody design and screening efficiency. In summary, this study contributes to the field by offering an innovative deep learning‐based method for antibody generation, addressing some limitations of traditional approaches, and underscoring the importance of integrating a specific antibody pretrained model and the biological properties of antibodies in generating novel sequences. The code and documentation underlying this article are freely available at https://github.com/zlfyj/AbDPP .