Prediction of Paratope-Epitope Pairs Using Convolutional Neural Networks

Antibodies play a central role in the adaptive immune response of vertebrates through the specific recognition of exogenous or endogenous antigens. The rational design of antibodies has a wide range of biotechnological and medical applications, such as in disease diagnosis and treatment. However, there are currently no reliable methods for predicting the antibodies that recognize a specific antigen region (or epitope) and, conversely, epitopes that recognize the binding region of a given antibody (or paratope). To fill this gap, we developed ImaPEp, a machine learning-based tool for predicting the binding probability of paratope-epitope pairs, where the epitope and paratope patches were simplified into interacting two-dimensional patches, which were colored according to the values of selected features, and pixelated. The specific recognition of an epitope image by a paratope image was achieved by using a convolutional neural network-based model, which was trained on a set of two-dimensional paratope-epitope images derived from experimental structures of antibody-antigen complexes. Our method achieves good performances in terms of cross-validation with a balanced accuracy of 0.8. Finally, we showcase examples of application of ImaPep, including extensive screening of large libraries to identify paratope candidates that bind to a selected epitope, and rescoring and refining antibody-antigen docking poses.