On the analysis of protein-protein interactions via knowledge-based potentials for the prediction of protein-protein docking

Development of effective methods to screen binary interactions obtained by rigid-body protein-protein docking is key for structure prediction of complexes and for elucidating physicochemical principles of protein-protein binding. We have derived empirical knowledge-based potential functions for selecting rigid-body docking poses. These potentials include the energetic component that provides the residues with a particular secondary structure and surface accessibility. These scoring functions have been tested on a state-of-art benchmark dataset and on a decoy dataset of permanent interactions. Our results were compared with a residue-pair potential scoring function (RPScore) and an atomic-detailed scoring function (Zrank). We have combined knowledge-based potentials to score protein-protein poses of decoys of complexes classified either as transient or as permanent protein-protein interactions. Being defined from residue-pair statistical potentials and not requiring of an atomic level description, our method surpassed Zrank for scoring rigid-docking decoys where the unbound partners of an interaction have to endure conformational changes upon binding. However, when only moderate conformational changes are required (in rigid docking) or when the right conformational changes are ensured (in flexible docking), Zrank is the most successful scoring function. Finally, our study suggests that the physicochemical properties necessary for the binding are allocated on the proteins previous to its binding and with independence of the partner. This information is encoded at the residue level and could be easily incorporated in the initial grid scoring for Fast Fourier Transform rigid-body docking methods.