Binding affinity prediction for antibody–protein antigen complexes: A machine learning analysis based on interface and surface areas

Specific antibodies can bind to protein antigens with high affinity and specificity, and this property makes them one of the best protein-based therapeutics. Accurate prediction of antibody‒protein antigen binding affinity is crucial for designing effective antibodies. The current predictive methods for protein‒protein binding affinity usually fail to predict the binding affinity of an antibody‒protein antigen complex with a comparable level of accuracy. Here, new models specific for antibody‒antigen binding affinity prediction are developed according to the different types of interface and surface areas present in antibody‒antigen complex. The contacts-based descriptors are also employed to construct or train different models specific for antibody‒protein antigen binding affinity prediction. The results of this study show that (i) the area-based descriptors are slightly better than the contacts-based descriptors in terms of the predictive power; (ii) the new models specific for antibody‒protein antigen binding affinity prediction are superior to the previously-used general models for predicting the protein‒protein binding affinities; (iii) the performances of the best area-based and contacts-based models developed in this work are better than the performances of a recently-developed graph-based model (i.e., CSM-AB) specific for antibody‒protein antigen binding affinity prediction. The new models developed in this work would not only help understand the mechanisms underlying antibody‒protein antigen interactions, but would also be of some applicable utility in the design and virtual screening of antibody-based therapeutics.