Identification of Surface Residues Involved in Protein-Protein Interaction — A Support Vector Machine Approach

Abstract

We describe a machine learning approach for sequence-based prediction of protein-protein interaction sites. . A support vector machine (SVM) classifier was trained to predict whether or not a surface residue is an interface residue (i.e., is located in the protein-protein interaction surface) based on the identity of the target residue and its 10 sequence neighbors. Separate classifiers were trained on proteins from two categories of complexes, antibody-antigen and protease-inhibitor. The effectiveness of each classifier was evaluated using leave-one-out (jack-knife) cross-validation. Interface and non-interface residues were classified with relatively high sensitivity (82.3% and 78.5%) and specificity (81.0% and 77.6%) for proteins in the antigen-antibody and protease inhibitor complexes, respectively. The correlation between predicted and actual labels was 0.430 and 0.462, indicating that the method performs substantially better than chance (zero correlation). Combined with recently developed methods for identification of surface residues from sequence information, this offers a promising approach to prediction of residues involved in protein-protein interaction from sequence information alone.