Accurate prediction of protein assembly structure by combining AlphaFold and symmetrical docking
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Abstract
AlphaFold can predict the structures of monomeric and multimeric proteins with high accuracy but has a limit on the number of chains and residues it can fold. Here we show that a combination of AlphaFold and all-atom symmetric docking simulations enables highly accurate prediction of the structure of complex symmetrical assemblies. We present a method to predict the structure of complexes with cubic - tetrahedral, octahedral and icosahedral - symmetry from sequence. Focusing on proteins where AlphaFold can make confident predictions on the subunit structure, 27 cubic systems were assembled with a median TM-score of 0.99 and a DockQ score of 0.72. 21 had TM-scores of above 0.9 and were categorized as acceptable- to high-quality according to DockQ. The resulting models are energetically optimized and can be used for detailed studies of intermolecular interactions in higher-order symmetrical assemblies. The results demonstrate how explicit treatment of structural symmetry can significantly expand the size and complexity of AlphaFold predictions.
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Preliminary reports suggest AF2 may predict oligomeric states of proteins and amyloids.
“Preliminary reports also suggest that AF2 may also be able to predict oligomeric states of proteins and amyloids17,57”
From The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins (2024) · cites this paper as [57]
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- [40]Jeppesen, M. & Andre, I. Accurate prediction of protein assembly structure by combining AlphaFold and symmetrical docking, EvoDOCK.10.5281/zenodo.10119213 (2023). PMC10719378 38092742 · DOI
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The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins
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“Preliminary reports also suggest that AF2 may also be able to predict oligomeric states of proteins and amyloids 17,57 .”
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“While many studies have examined AF-M’s ability to correctly predict structures in curated PPI databases 25–27 , there has been less focus on separating true from false interactions in large-scale unbiased screens.”
- Authors
- Jeppesen, M., & André, I.
- Affiliations
- Lund University (SE)
- Corresponding author
- André, Ingemar
- Venue
- Nature Communications
- Published
- 2023-12-13
- Volume
- 14
- Issue
- 1
- Pages
- 8283-8283
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10719378
- OpenAlex
- W4389686140
- Cited by
- 44
- References
- 39
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 13 · 2023: 1
- FWCI
- 3.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- European Commission (HORIZON2020, 771820)
- Lunds Universitet
- 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
- AlphaFold, cubic symmetry, tetrahedral symmetry, octahedral symmetry, icosahedral symmetry, structural symmetry, multimeric proteins, TM-score, intermolecular interactions
- MeSH terms
- Protein Conformation, Proteins
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