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CryoSTAR: leveraging structural priors and constraints for cryo-EM heterogeneous reconstruction
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Abstract
Resolving conformational heterogeneity in cryogenic electron microscopy datasets remains an important challenge in structural biology. Previous methods have often been restricted to working exclusively on volumetric densities, neglecting the potential of incorporating any preexisting structural knowledge as prior or constraints. Here we present cryoSTAR, which harnesses atomic model information as structural regularization to elucidate such heterogeneity. Our method uniquely outputs both coarse-grained models and density maps, showcasing the molecular conformational changes at different levels. Validated against four diverse experimental datasets, spanning large complexes, a membrane protein and a small single-chain protein, our results consistently demonstrate an efficient and effective solution to conformational heterogeneity with minimal human bias. By integrating atomic model insights with cryogenic electron microscopy data, cryoSTAR represents a meaningful step forward, paving the way for a deeper understanding of dynamic biological processes.
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Metadata
- Authors
- Li, Y., Zhou, Y., Yuan, J., Ye, F., & Gu, Q.
- Affiliations
- ByteDance (China) (CN)
- Corresponding author
- Gu, Quanquan
- Venue
- Nature Methods
- Published
- 2024-10-29
- Volume
- 21
- Issue
- 12
- Pages
- 2318-2326
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- OpenAlex
- W4403873534
- Cited by
- 20
- References
- 3
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 2
- FWCI
- 3.66
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Methods (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- 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
- Keywords
- conformational heterogeneity, structural priors, coarse-grained models, density maps, deep neural network, membrane proteins, single-chain protein
- MeSH terms
- Algorithms, Humans, Image Processing, Computer-Assisted, Models, Molecular, Protein Conformation, Software, Cryoelectron Microscopy
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