Abstract
SUMMARY: The ability to predict antibody-antigen binding is essential for computational models of antibody affinity maturation and protein design. While most models aim to predict binding for arbitrary antigens and antibodies, the global impact of SARS-CoV-2 on public health and the availability of associated data suggest that a SARS-CoV-2-specific model would be highly beneficial. In this work, we present a neural network model, trained on ∼315 000 datapoints from deep mutational scanning experiments, that predicts escape fractions of SARS-CoV-2 RBDs binding to arbitrary antibodies. The antibody embeddings within the model constitute an effective sequence space, which correlates with the Hamming distance, suggesting that these embeddings may be useful for downstream tasks such as binding prediction. Indeed, the model achieves Spearman correlation coefficients of 0.46 and 0.52 on two held-out test sets. By comparison, correlation coefficients calculated using existing structure and sequence-based models do not exceed 0.28. The correlation coefficient against dissociation constants of antibodies binding to SARS-CoV-2 RBD variants is 0.46. Additionally, the residue-level escapes are highest in the antibody epitope, correlating well with experimentally measured escapes. We further study the effect of antibody chain use, embedding dimension size and feed-forward and convolutional architectures on the model results. Lastly, we find that the inference time of our model is significantly faster than previous models, suggesting that it could be a useful tool for the accurate and rapid prediction of antibodies binding to SARS-CoV-2 RBDs. AVAILABILITY AND IMPLEMENTATION: The model and associated code are available for download at https://github.com/ericzwang/RBD_AB. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics Advances online.