Joël Janin

The Critical Assessment of PRedicted Interactions (CAPRI) experiment was designed in 2000 to test protein docking algorithms in blind predictions of the structure of protein–protein complexes. In four years, 17 complexes offered by crystallographers as targets prior to publication, have been subjected to structure prediction by docking their two components. Models of these complexes were submitted by predictor groups and assessed by comparing their geometry to the X‐ray structure and by evaluating the quality of the prediction of the regions of interaction and of the pair wise residue contacts. Prediction was successful on 12 of the 17 targets, most of the failures being due to large conformation changes that the algorithms could not cope with. Progress in the prediction quality observed in four years indicates that the experiment is a powerful incentive to develop new procedures that allow for flexibility during docking and incorporate nonstructural information. We therefore call upon structural biologists who study protein–protein complexes to provide targets for further rounds of CAPRI predictions.

The subunit interfaces of 122 homodimers of known three‐dimensional structure are analyzed and dissected into sets of surface patches by clustering atoms at the interface; 70 interfaces are single‐patch, the others have up to six patches, often contributed by different structural domains. The average interface buries 1,940 Ų of the surface of each monomer, contains one or two patches burying 600–1,600 Ų, is 65% nonpolar and includes 18 hydrogen bonds. However, the range of size and of hydrophobicity is wide among the 122 interfaces. Each interface has a core made of residues with atoms buried in the dimer, surrounded by a rim of residues with atoms that remain accessible to solvent. The core, which constitutes 77% of the interface on average, has an amino acid composition that resembles the protein interior except for the presence of arginine residues, whereas the rim is more like the protein surface. These properties of the interfaces in homodimers, which are permanent assemblies, are compared to those of protein‐protein complexes where the components associate after they have independently folded. On average, subunit interfaces in homodimers are twice larger than in complexes, and much less polar due to the large fraction belonging to the core, although the amino acid compositions of the cores are similar in the two types of interfaces. Proteins 2003.

Three-dimensional structures are known from X-ray studies of the nucleoside diphosphate(NDP) kinase of many organisms from bacteria to human. All NDP kinases have subunits ofabout 150 residues with a...