Deep Geometric Framework to Predict Antibody-Antigen Binding Affinity

Abstract

In drug development, the efficacy of an antibody depends on how the antibody interacts with the target antigen. The strength of these interactions gives an indication of how successful an antibody is in neutralizing an antigen. Therefore, the strength, measured by "binding affinity", is a critical aspect of antibody engineering. In theory, the higher the binding affinity, the higher the chances are that the antibody is successful against the target antigen. Currently, techniques such as molecular docking and molecular dynamics are utilized in quantifying the binding affinity. However, owing to the computational complexity of the aforementioned techniques, running simulations for large antibodies/antigens remains a daunting task. Despite the commendable improvements in deep learning-based binding affinity prediction, such approaches are highly dependent on the quality of the antibody-antigen structures and they tend to overlook the importance of capturing the evolutionary details of proteins upon mutation. Further, most of the existing datasets for the task only include antibody-antigen pairs related to one antigen variant and, thus, are not suitable for developing comprehensive data-driven approaches. To circumvent the said complexities, we first curate the largest and most generalized datasets for antibody-antigen binding affinity prediction, consisting of both protein sequences and structures. Subsequently, we propose a deep geometric neural network comprising a structure-based model and a sequence-based model that considers both atomistic and evolutionary details when predicting the binding affinity. The proposed framework exhibited a 10% improvement in mean absolute error compared to the state-of-the-art models while showing a strong correlation between the predictions and target values. We release the datasets and code publicly (https://drug-discovery-entc.github.io/p2pxml/) to support the development of antibody-antigen binding affinity prediction frameworks for the benefit of science and society.