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Exploring the Potential of AlphaFold Distograms for Predicting Binding-induced Hinge Motions
Open accessPreprint — published as 10.1002/1873-3468.70297
Abstract
AlphaFold models provide static structural predictions, limiting their use in interpreting flexible regions in low-resolution cryo-EM maps. Here, we assess whether AlphaFold-generated distograms can instead reveal conformational flexibility, focusing on binding-induced hinge motions. For this, we examined the key metabolic AK2/AIFM1 complex, where molecular dynamics and cryo-EM confirm a hinge motion in AK2 upon binding. Notably, this motion is captured in the AlphaFold2/3 distograms of apo AK2, even though it is absent in the predicted structures. By extending our analysis to other systems, we demonstrate that distograms may offer a valuable, model-independent method for interpreting ambiguous regions in cryo-EM maps.
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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Predicting multiple conformations via sequence clustering and AlphaFold2
Wayment-Steele, H. K., Ojoawo, A., Otten, R., Apitz, J. M., Pitsawong, W., Hömberger, M., Ovchinnikov, S., Colwell, L., & Kern, D. (2024) · Nature · doi:10.1038/s41586-023-06832-9 · Cited by 545
Sampling alternative conformational states of transporters and receptors with AlphaFold2
del Alamo, D., Sala, D., Mchaourab, H. S., & Meiler, J. (2022) · eLife · doi:10.7554/elife.75751 · Cited by 511
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Metadata
- Authors
- Savaş, B., Barlas, A. B., & Karaca, E.
- Affiliations
- Dokuz Eylül University (TR)
- Corresponding author
- Karaca, Ezgi
- Venue
- FEBS Letters
- Publisher
- openRxiv
- Published
- 2025-07-27
- Volume
- 600
- Issue
- 10
- Pages
- 1558-1570
- ISSN
- 0014-5793 (ISSN-L)
- OpenAlex
- W7127579793
- Cited by
- 5
- References
- 3
- Citations by year
- 2026: 3 · 2025: 2
- FWCI
- 6.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- EMBO (Installation Grant 4421)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Keywords
- hinge motion, conformational flexibility, protein-protein binding, apo structure, protein structure prediction
- MeSH terms
- Models, Molecular, Motion, Protein Binding, Protein Conformation, Cryoelectron Microscopy, Molecular Dynamics Simulation
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