How to choose templates for modeling of protein complexes: Insights from benchmarking template-based docking
Open accessAbstract
Comparative docking is based on experimentally determined structures of protein-protein complexes (templates), following the paradigm that proteins with similar sequences and/or structures form similar complexes. Modeling utilizing structure similarity of target monomers to template complexes significantly expands structural coverage of the interactome. Template-based docking by structure alignment can be performed for the entire structures or by aligning targets to the bound interfaces of the experimentally determined complexes. Systematic benchmarking of docking protocols based on full and interface structure alignment showed that both protocols perform similarly, with top 1 docking success rate 26%. However, in terms of the models' quality, the interface-based docking performed marginally better. The interface-based docking is preferable when one would suspect a significant conformational change in the full protein structure upon binding, for example, a rearrangement of the domains in multidomain proteins. Importantly, if the same structure is selected as the top template by both full and interface alignment, the docking success rate increases 2-fold for both top 1 and top 10 predictions. Matching structural annotations of the target and template proteins for template detection, as a computationally less expensive alternative to structural alignment, did not improve the docking performance. Sophisticated remote sequence homology detection added templates to the pool of those identified by structure-based alignment, suggesting that for practical docking, the combination of the structure alignment protocols and the remote sequence homology detection may be useful in order to avoid potential flaws in generation of the structural templates library.
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Such flexibility limits the applicability of structure-alignment-based comparative docking and significantly increases the dimensionality of the docking search space by adding the multiplicity of internal degrees of freedom of the non-protein component.
“Such flexibility limits the applicability of the powerful structure-alignment-based comparative docking [19] and significantly increases the dimensionality of the docking search space by adding the multiplicity of the internal degrees of freedom of the non-protein component.”
From Challenges in protein docking (2020) · cites this paper as [19]
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- Authors
- Chakravarty, D., McElfresh, G., Kundrotas, P. J., & Vakser, I. A.
- Affiliations
- University of Kansas (US)
- Corresponding author
- Kundrotas, Petras J.
- Vakser, Ilya A.
- Venue
- Proteins Structure Function and Bioinformatics
- Publisher
- Wiley
- Published
- 2020-02-07
- Volume
- 88
- Issue
- 8
- Pages
- 1070-1081
- ISSN
- 0887-3585 (ISSN-L)
- 1097-0134
- PMC
- PMC7375009
- OpenAlex
- W3003966498
- Cited by
- 13
- References
- 55
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 3
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Proteins Structure Function and Bioinformatics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01GM074255)
- National Science Foundation (DBI1565107, DBI1917263)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- template-based docking, protein-protein complex, structural alignment, structural templates, multidomain proteins, protein-protein interaction prediction
- MeSH terms
- Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Amino Acid Sequence, Animals, Binding Sites, Dogs, Escherichia coli, Humans, Ligands, Peptides, Protein Binding, Proteins, Research Design, Software, Thermodynamics, Benchmarking, Protein Interaction Mapping, Structural Homology, Protein, Protein Interaction Domains and Motifs, Protein Multimerization, Molecular Docking Simulation
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