ProAffiMuSeq: sequence-based method to predict the binding free energy change of protein-protein complexes upon mutation using functional classification

Motivation: Protein-protein interactions are essential for the cell and mediate various functions. However, mutations can disrupt these interactions and may cause diseases. Currently available computational methods require a complex structure as input for predicting the change in binding affinity. Further, they have not included the functional class information for the protein-protein complex. To address this, we have developed a method, ProAffiMuSeq, which predicts the change in binding free energy using sequence-based features and functional class. Results: Our method shows an average correlation between predicted and experimentally determined Delta Delta G of 0.73 and mean absolute error (MAE) of 0.86 kcal/mol in 10-fold cross-validation and correlation of 0.75 with MAE of 0.94 kcal/mol in the test dataset. ProAffiMuSeq was also tested on an external validation set and showed results comparable to structure-based methods. Our method can be used for large-scale analysis of disease-causing mutations in protein-protein complexes without structural information.