Protein-Protein Complex Structure Predictions by Multimeric Threading and Template Recombination
Open accessAbstract
The total number of protein-protein complex structures currently available in the Protein Data Bank (PDB) is six times smaller than the total number of tertiary structures in the PDB, which limits the power of homology-based approaches to complex structure modeling. We present a threading-recombination approach, COTH, to boost the protein complex structure library by combining tertiary structure templates with complex alignments. The query sequences are first aligned to complex templates using a modified dynamic programming algorithm, guided by ab initio binding-site predictions. The monomer alignments are then shifted to the multimeric template framework by structural alignments. COTH was tested on 500 nonhomologous dimeric proteins, which can successfully detect correct templates for 50% of the cases after homologous templates are excluded, which significantly outperforms conventional homology modeling algorithms. It also shows a higher accuracy in interface modeling than rigid-body docking of unbound structures from ZDOCK although with lower coverage. These data demonstrate new avenues to model complex structures from nonhomologous templates.
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Template-based methods for predicting protein complex structures utilize experimentally resolved multimeric structures.
“A second class of approaches is template-based methods, which utilize experimentally resolved multimeric structures12–16.”
From AF2Complex predicts direct physical interactions in multimeric proteins with deep learning (2022) · cites this paper as [16]
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- Authors
- Mukherjee, S., & Zhang, Y.
- Affiliations
- University of Kansas (US)
- Corresponding author
- Zhang, Yang
- ORCID
- Zhang, Yang
- Venue
- Structure
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 19
- Issue
- 7
- Pages
- 955-966
- ISSN
- 0969-2126 (ISSN-L)
- PMC
- PMC3134792
- OpenAlex
- W2139373949
- Cited by
- 174
- References
- 51
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 7 · 2023: 11 · 2022: 13 · 2021: 16 · 2020: 10 · 2019: 17 · 2018: 6 · 2017: 14 · 2016: 18 · 2015: 12 · 2014: 15 · 2013: 14 · 2012: 8
- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Structure (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation
- National Institute of General Medical Sciences (GM-083107, R01GM084222, GM-084222, R01GM083107)
- 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
- protein-protein complex structure prediction, homology modeling, binding site prediction, structural alignment, dimeric protein, interface modeling, rigid-body docking
- MeSH terms
- Algorithms, Animals, Binding Sites, Humans, Models, Molecular, Protein Binding, Protein Conformation, Proteins, Software, Protein Folding, Computational Biology, Protein Interaction Mapping, Databases, Protein, Protein Multimerization
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