AREA-AFFINITY: A Web Server for Machine Learning-Based Prediction of Protein–Protein and Antibody–Protein Antigen Binding Affinities

[Image: see text] Protein–Protein binding affinity reflects the binding strength between the binding partners. The prediction of protein–protein binding affinity is important for elucidating protein functions and also for designing protein-based therapeutics. The geometric characteristics such as area (both interface and surface areas) in the structure of a protein–protein complex play an important role in determining protein–protein interactions and their binding affinity. Here, we present a free web server for academic use, AREA-AFFINITY, for prediction of protein–protein or antibody–protein antigen binding affinity based on interface and surface areas in the structure of a protein–protein complex. AREA-AFFINITY implements 60 effective area-based protein–protein affinity predictive models and 37 effective area-based models specific for antibody–protein antigen binding affinity prediction developed in our recent studies. These models take into consideration the roles of interface and surface areas in binding affinity by using areas classified according to different amino acid types with different biophysical nature. The models with the best performances integrate machine learning methods such as neural network or random forest. These newly developed models have superior or comparable performance compared to the commonly used existing methods. AREA-AFFINITY is available for free at: https://affinity.cuhk.edu.cn/.