Modeling protein–protein and protein–peptide complexes: CAPRI 6th edition

• Published in: Proteins, structure, function, and bioinformatics Vol. 85; no. 3; pp. 359 - 377
• Main Authors: Lensink, Marc F., Velankar, Sameer, Wodak, Shoshana J.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.03.2017
• Series: Proteins
• Subjects: Algorithms; Benchmarking; Binding Sites; blind prediction; capri; Chemical Sciences; Computational Biology - methods; Computer applications; Docking; Evaluation; Humans; Kinases; Model accuracy; Molecular conformation; Molecular Docking Simulation; Multiprotein Complexes - chemistry; Nucleosomes - chemistry; or physical chemistry; Peptides; Peptides - chemistry; Predictions; Protein Binding; Protein Conformation; protein docking; Protein Interaction Mapping - methods; Protein Interaction Mapping - statistics & numerical data; Protein structure; Proteins; Proteins - chemistry; protein–peptide interation; Research Design; Software; Theoretical and; Water - chemistry; water modeling; capri; protein-peptide interation; blind prediction; protein docking; water modeling; Water; Peptides; Humans; Multiprotein Complexes; Computational Biology; Benchmarking; Protein Interaction Mapping; Proteins; Algorithms; Capri; Protein Binding; Blind prediction; Protein Conformation; Nucleosomes; Molecular Docking Simulation; Software; Binding Sites; Research Design
• ISSN: 0887-3585; 1097-0134; 1097-0134
• DOI: 10.1002/prot.25215

ABSTRACT We present the sixth report evaluating the performance of methods for predicting the atomic resolution structures of protein complexes offered as targets to the community‐wide initiative on the Critical Assessment of Predicted Interactions (CAPRI). The evaluation is based on a total of 20,670 predicted models for 8 protein–peptide complexes, a novel category of targets in CAPRI, and 12 protein–protein targets in CAPRI prediction Rounds held during the years 2013‐2016. For two of the protein–protein targets, the focus was on the prediction of side‐chain conformation and positions of interfacial water molecules. Seven of the protein–protein targets were particularly challenging owing to their multicomponent nature, to conformational changes at the binding site, or to a combination of both. Encouragingly, the very large multiprotein complex with the nucleosome was correctly predicted, and correct models were submitted for the protein–peptide targets, but not for some of the challenging protein–protein targets. Models of acceptable quality or better were obtained for 14 of the 20 targets, including medium quality models for 13 targets and high quality models for 8 targets, indicating tangible progress of present‐day computational methods in modeling protein complexes with increased accuracy. Our evaluation suggests that the progress stems from better integration of different modeling tools with docking procedures, as well as the use of more sophisticated evolutionary information to score models. Nonetheless, adequate modeling of conformational flexibility in interacting proteins remains an important area with a crucial need for improvement. Proteins 2017; 85:359–377. © 2016 Wiley Periodicals, Inc.