Docking Predictions of Protein-Protein Interactions and Their Assessment: The CAPRI Experiment
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Protein-protein docking was born in the 1970s as a tool to analyze macromolecular recognition. It developed afterwards into a method of prediction of the mode of association between proteins of known structure. Since 2001, the performance of docking procedures has been assessed in blind predictions by the CAPRI (Critical Assessment of PRedicted Interactions) experiment. The results show that docking routinely yields good models of the protein-protein complexes that undergo only minor changes in conformation and associate as rigid bodies. In contrast, flexible recognition accompanying large conformation changes in the components remains difficult to simulate, and structural predictions generally yield lower quality models. In recent years, a new challenge has been to predict affinity and to estimate the stability of the complex along with its structure. Over the years, CAPRI has proved to be a strong incentive to develop new flexible docking procedures and more discriminative scoring functions, and it has provided a common ground for discussing methods and questions related to protein-protein recognition.
KeywordsCommunity-wide experiment Protein-protein recognition Binding affinity Protein flexibility Protein engineering Docking simulation Computational biology DOCK CAPRI Rigid body docking Cube representation Geometric hashing algorithm Monte-Carlo RosettaDock Template-based docking CASP Blind prediction Flexible docking Molecular dynamics Flexibility Affinity benchmark
JJ acknowledges a long term collaboration with Pr. Shoshana Wodak (Free University, Brussels, and University of Toronto), fostered in its early days by Dr. Georges Cohen (Institut Pasteur, Paris), the European Molecular Biology Organisation, and Centre Européen de Calcul Atomique et Moléculaire. The CAPRI experiment owes much to R. Mendez and M. Lensink who perform the assessment together with S. Wodak, to K. Henrick and S. Velenkar who manage its Web site at the European Bioinformatics Institute (Hinxton, UK), to J. Moult, S. Vajda, I. Vakser, M. Sternberg, and L. Ten Eyck, who assist in its management, and to all the structural biologists who have contributed targets.
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