Prediction of homo- and hetero-protein complexes by protein docking and template-based modeling: a CASP-CAPRI experiment

By Marc F. Lensink, S. Velankar, Andriy Kryshtafovych, Shengua Huang, Dina Schneidman-Duhovny, Andrej Sali, J. Segura, N. Fernández-Fuentes, Shruthi Viswanath, R. Elber and 92 more. 2016

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We present the results for CAPRI Round 30, the first joint CASP‐CAPRI experiment, which brought together experts from the protein structure prediction and protein–protein docking communities. The Round comprised 25 targets from amongst those submitted for the CASP11 prediction experiment of 2014. The targets included mostly homodimers, a few homotetramers, and two heterodimers, and comprised protein chains that could readily be modeled using templates from the Protein Data Bank. On average 24 CAPRI groups and 7 CASP groups submitted docking predictions for each target, and 12 CAPRI groups per target participated in the CAPRI scoring experiment. In total more than 9500 models were assessed against the 3D structures of the corresponding target complexes. Results show that the prediction of homodimer assemblies by homology modeling techniques and docking calculations is quite successful for targets featuring large enough subunit interfaces to represent stable associations. Targets with ambiguous or inaccurate oligomeric state assignments, often featuring crystal contact‐sized interfaces, represented a confounding factor. For those, a much poorer prediction performance was achieved, while nonetheless often providing helpful clues on the correct oligomeric state of the protein. The prediction performance was very poor for genuine tetrameric targets, where the inaccuracy of the homology‐built subunit models and the smaller pair‐wise interfaces severely limited the ability to derive the correct assembly mode. Our analysis also shows that docking procedures tend to perform better than standard homology modeling techniques and that highly accurate models of the protein components are not always required to identify their association modes with acceptable accuracy. Proteins 2016; 84(Suppl 1):323–348. © 2016 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

Subfields: Computational Theory and Mathematics, Materials Chemistry, Molecular Biology

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Citations in the corpus

Critical Assessment of Methods of Protein Structure Prediction (CASP) – Round XII (2017, methodology): “In round 11, CASP increased the emphasis on assembly structures by extending the targets to include heteromeric complexes and by collaborating with CAPRI to address this area.(34,35) The area was further strengthened in CASP12 by introducing a separate category in which the accuracy of the predicted”
Blind prediction of homo- and hetero-protein complexes: The CASP13-CAPRI experiment (2019, positive): “40,41 To help tackle these more difficult cases, 3D models of the target proteins (mainly those of individual subunits) predicted by participating CASP servers were made available to all predictor groups (of both CASP and CAPRI), 1 week into the prediction round, and a good number of CAPRI groups…”
Flexible backbone assembly and refinement of symmetrical homomeric complexes (2018, background): “In the last published rounds of the blind docking challenge, Critical Assessment of PRediction of Interactions (CAPRI), although multiple groups generated high-quality models for various homodimers, no group was able to predict high-quality models for the five homotetramer targets, including two for”
Assessment of protein assembly prediction in CASP12 (2018, background): “11 Although the participation of CASP groups stayed low, with only five groups submitting oligomeric models for more than half of the 17 CASP oligomeric targets included in the CAPRI assessment, four of them submitted accurate models by CAPRI standards.”
Small angle X-ray scattering and cross-linking for data assisted protein structure prediction in CASP 12 with prospects for improved accuracy (2018, background): “Also, CASP-CAPRI reported ambiguous and even inaccurate assignments of oligomerization interfered with their docking assessments.(39) Here, 3 of the SAXS-determined multimerizations appear biologically relevant, where contacts between multimers are important for maintaining folds in those regions.”
InterEvDock2: an expanded server for protein docking using evolutionary and biological information from homology models and multimeric inputs (2018, background): “Although the InterEvDock2 pipeline was not specifically designed to handle homo-oligomeric docking, we were also among the highest ranking groups in the two joint CASPCAPRI experiments involving mostly predictions of homodimers (46,47).”
Pre‐ and post‐docking sampling of conformational changes using ClustENM and HADDOCK for protein‐protein and protein‐DNA systems (2019, methodology): “…use HADDOCK, 14-16 an information-driven approach for the modeling of biomolecular complexes, which has demonstrated sustained performance in CAPRI - the blind modeling experiment for the prediction of complexes, 17,18 and is a widely used method for integrative modeling of biomolecular complexes.”
Prediction of protein assemblies, the next frontier: The CASP14-CAPRI experiment (2021, methodology): “On the basis of the values of these three parameters models are ranked into four categories: high quality, medium quality, acceptable quality, and incorrect, as previously described.(38)”
Automatic structure prediction of oligomeric assemblies using Robetta in CASP12 (2017, methodology): “From these experiments, and subsequent tuning in CAMEO,(17) it was found that: (1) considering the top 3 templates from each template detection and sequence alignment method, (2) skipping symmetry detection in cases with target_difficulty<0.”
Harnessing protein folding neural networks for peptide–protein docking (2021, methodology): “For the models to be comparable via other community-wise used metrics, CAPRI interface metrics (65) were also extracted from the calculated scores (see Supplementary Figure S2).”
Efficient Flexible Backbone Protein-Protein Docking for Challenging Targets (2017, background): “The most recent rounds of the blind docking challenge, Critical Assessment of PRediction of Interactions (CAPRI), demonstrated that protein flexibility is still a community-wide weakness, with flexible target complexes eliciting no successful predictions from any method (16, 17).”
The HDOCK server for integrated protein–protein docking (2020, methodology): “…as building structures from sequences, incorporating binding interface information and running docking commands, although our docking protocol achieved an excellent performance in the multimeric protein structure prediction in the community-wide CASP11-CAPRI and CASP12-CAPRI experiments 21,25,26 .”
A Comprehensive Review on Current Advances in Peptide Drug Development and Design (2019, background): “Recently, CAPRI experiments revealed that a hybrid model selection methodology of utilizing both energy-based scoring as well as other methods such as mutagenesis, co-evolutionary information, sequence- or structural-clustering function could generate accurate peptide–protein docking results that ar”
The challenge of modeling protein assemblies: the CASP12‐CAPRI experiment (2018, methodology): “For each of these targets the distinct interfaces were identified on the basis of the author-defined biological unit, and predicted models were evaluated by comparing in turn each pair of distinct interacting subunits in the model to each of the relevant pairs of interacting subunits in the target, ”