Assessment of blind predictions of protein–protein interactions: Current status of docking methods
- 13 May 2003
- journal article
- research article
- Published by Wiley in Proteins-Structure Function and Bioinformatics
- Vol. 52 (1), 51-67
- https://doi.org/10.1002/prot.10393
Abstract
The current status of docking procedures for predicting protein–protein interactions starting from their three‐dimensional structure is assessed from a first major evaluation of blind predictions. This evaluation was performed as part of a communitywide experiment on Critical Assessment of PRedicted Interactions (CAPRI). Seven newly determined structures of protein–protein complexes were available as targets for this experiment. These were the complexes between a kinase and its protein substrate, between a T‐cell receptor β‐chain and a superantigen, and five antigen‐antibody complexes. For each target, the predictors were given the experimental structures of the free components, or of one free and one bound component in a random orientation. The structure of the complex was revealed only at the time of the evaluation. A total of 465 predictions submitted by 19 groups were evaluated. These groups used a wide range of algorithms and scoring functions, some of which were completely novel. The quality of the predicted interactions was evaluated by comparing residue–residue contacts and interface residues to those in the X‐ray structures and by analyzing the fit of the ligand molecules (the smaller of the two proteins in the complex) or of interface residues only, in the predicted versus target complexes. A total of 14 groups produced predictions, ranking from acceptable to highly accurate for five of the seven targets. The use of available biochemical and biological information, and in one instance structural information, played a key role in achieving this result. It was essential for identifying the native binding modes for the five correctly predicted targets, including the kinase‐substrate complex where the enzyme changes conformation on association. But it was also the cause for missing the correct solution for the two remaining unpredicted targets, which involve unexpected antigen‐antibody binding modes. Overall, this analysis reveals genuine progress in docking procedures but also illustrates the remaining serious limitations and points out the need for better scoring functions and more effective ways for handling conformational flexibility. Proteins 2003;52:51–67.Keywords
Funding Information
- Marie Curie Host Training (QLK3-1999-51297)
This publication has 46 references indexed in Scilit:
- A comprehensive two-hybrid analysis to explore the yeast protein interactomeProceedings of the National Academy of Sciences, 2001
- Mapping protein family interactions: intramolecular and intermolecular protein family interaction repertoires in the PDB and yeast11Edited by J. KarnJournal of Molecular Biology, 2001
- The atomic structure of protein-protein recognition sites 1 1Edited by A. R. FershtJournal of Molecular Biology, 1999
- Modelling protein docking using shape complementarity, electrostatics and biochemical information 1 1Edited by J. ThorntonJournal of Molecular Biology, 1997
- Protein docking and complementarityJournal of Molecular Biology, 1991
- “Soft docking”: Matching of molecular surface cubesJournal of Molecular Biology, 1991
- The BRUGEL package: toward computer-aided design of macromoleculesJournal of Molecular Graphics, 1988
- Interactive program for visualization and modelling of proteins, nucleic acids and small moleculesJournal of Molecular Graphics, 1986
- Gene duplications in the structural evolution of chymotrypsinJournal of Molecular Biology, 1979
- Computer analysis of protein-protein interactionJournal of Molecular Biology, 1978