Next challenges in protein-protein docking: from proteome to interactome and beyond

Advances in biophysics and biochemistry have pushed back the limits for the structural characterization of biomolecular assemblies. Large efforts have been devoted to increase both resolution and accuracy of the methods, probe into the smallest biomolecules as well as the largest macromolecular machineries, unveil transient complexes along with dynamic interaction processes, and, lately, dissect whole organism interactomes using high-throughput strategies. However, the atomic description of such interactions, rarely reached by large-scale projects in structural biology, remains indispensable to fully understand the subtleties of the recognition process, measure the impact of a mutation or predict the effect of a drug binding to a complex. Mixing even a limited amount of experimental and/or bioinformatic data with modeling methods, such as macromolecular docking, presents a valuable strategy to predict the three-dimensional structures of complexes. Recent developments indicate that the docking community is seething to tackle the greatest challenge of adding the structural dimension to interactomes. (C) 2011 John Wiley & Sons, Ltd.