Predicting Protein-Protein Binding Affinity by In silico Docking

Protein-protein interactions, which result in either transient or long-lived complexes, play a central role in the processes happening in the cells. Perturbations in those interaction networks can lead to disease. Understanding the mechanisms of proteinprotein binding is inherently difficult due to the range of potential interactions, the molecular rearrangement associated with binding, and the time and length scales involved. In silico protein docking is a valuable tool in determination of the structures of protein–protein complexes that complements experimental methods with a level of details that are unattainable in experiment. Although the precise prediction of the structure of protein-protein complex is sufficient to describe the interaction in atomic details, it is the knowledge of affinity of the components for each other is necessary for the prediction of the existence of this assembly and whether it is transient or permanent. Recently, a structure-based binding affinity benchmark Version 1.0, which includes a non redundant set of 144 protein–protein complexes that have highresolution structures available for both the complexes and their unbound components, and for which dissociation constants have been measured by biophysical methods, and the updated version, which contains 179 entries, have been presented. Because for all protein complexes in this benchmark the unbound structures of component proteins are available, these benchmarks allow for the assessment of conformational changes upon protein-protein binding. We use this assessment together with experimental data to explain failures and successes in prediction structures and affinity by in silico docking using the combination of rigid docking and RosettaDock refinements.