The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Conformational space exploration of cryo-EM structures by variability refinement
Open accessPreprint — published as 10.1016/j.bbamem.2023.184133 · Paper page
Abstract
Summary: Cryo-EM observation of biological samples enables visualization of sample heterogeneity, in the form of discrete states that are separatable, or continuous heterogeneity as a result of local protein motion before flash freezing. Variability analysis of this continuous heterogeneity describes the variance between a particle stack and a volume, and results in a map series describing the various steps undertaken by the sample in the particle stack. While this observation is absolutely stunning, it is very hard to pinpoint structural details to elements of the maps. In order to bridge the gap between observation and explanation, we designed a tool that refines an ensemble of structures into all the maps from variability analysis. Using this bundle of structures, it is easy to spot variable parts of the structure, as well as the parts that are not moving. Comparison with molecular dynamics simulations highlight the fact that the movements follow the same directions, albeit with different amplitudes. Ligand can also be investigated using this method. Variability refinement is available in the Phenix software suite, accessible under the program name phenix . varref .
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Flagged first, then by citations
Research works printed but not linked: 38
- 10.1080/0889311X.2013.835806 · DOI
- 10.1107/S0021889805038987 · DOI
- 2015, Ensemble Calculation for Intrinsically Disordered Proteins Using NMR Parameters, Adv Exp Med Biol, 870, 123, 10.1007/978-3-319-20164-1_4 · DOI
- 2017, Applications of solid-state NMR to membrane proteins, Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 1865, 1577, 10.1016/j.bbapap.2017.07.004 · DOI
- Lecoq, L. , et al., Solid-State NMR for Studying the Structure and Dynamics of Viral Assemblies. Viruses, 2020. 12(10). · DOI
- 10.1038/s41467-021-24651-2 · DOI
- 10.1038/s41586-019-1391-0 · DOI
- 10.1016/j.jsb.2021.107702 · DOI
- Ludtke, S.J. , Chapter Seven - Single-Particle Refinement and Variability Analysis in EMAN2. 1, in Methods in Enzymology, R.A. Crowther , Editor. 2016, Academic Press. p. 159–189. · DOI
- 2021, A set of common movements within GPCR-G-protein complexes from variability analysis of cryo-EM datasets, Journal of Structural Biology, 213, 107699, 10.1016/j.jsb.2021.107699 · DOI
- 2021, CryoDRGN: reconstruction of heterogeneous cryo-EM structures using neural networks, Nature Methods, 18, 176, 10.1038/s41592-020-01049-4 · DOI
- 10.7554/eLife.36861 · DOI
- 10.1016/j.ymeth.2011.07.005 · DOI
- 2018, New tools for the analysis and validation of cryo-EM maps and atomic models, Acta Crystallographica Section D, 74, 814, 10.1107/S2059798318009324 · DOI
- 2018, Real-space refinement in PHENIX for cryo-EM and crystallography, Acta Crystallographica Section D, 74, 531, 10.1107/S2059798318006551 · DOI
- 2007, Interpretation of ensembles created by multiple iterative rebuilding of macromolecular models, Acta Crystallographica Section D, 63, 597, 10.1107/S0907444907009791 · DOI
- 10.1038/nmeth.4169 · DOI · Paper page
- 2021, Multidrug Resistance in Mammals and Fungi—From MDR to PDR: A Rocky Road from Atomic Structures to Transport Mechanisms, International Journal of Molecular Sciences, 22, 4806, 10.3390/ijms22094806 · DOI
- 10.1146/annurev-biochem-011520-105201 · DOI
- 10.1111/j.1574-6968.2010.02143.x · DOI
- 10.1021/bi702303s · DOI
- 10.1021/bi0362018 · DOI
- He, J. , et al., Pleiotropic Roles of ABC Transporters in Breast Cancer. Int J Mol Sci, 2021. 22(6). · DOI
- 10.20892/j.issn.2095-3941.2019.0284 · DOI
- 10.1093/jac/dkq279 · DOI
- 10.1016/S1471-4914(02)02280-3 · DOI · Paper page
- 2018, Relative Contribution of the ABC Transporters Cdr1, Pdh1, and Snq2 to Azole Resistance in Candida glabrata, Antimicrobial Agents and Chemotherapy, 62, e01070
- 10.1128/AAC.05546-11 · DOI
- 10.1146/annurev.biochem.78.082907.145923 · DOI
- 2016, Placental ABC Transporters: Biological Impact and Pharmaceutical Significance, Pharm Res, 33, 2847, 10.1007/s11095-016-2028-8 · DOI
- Chaves, C. , et al., Human ABC Transporters at blood-CNS Interfaces as Determinants of CNS Drug Penetration. Curr Pharm Des, 2013. · DOI
- 10.1038/nrd1984 · DOI · Paper page
- 2022, Substrate-bound and substrate-free outward-facing structures of a multidrug ABC exporter, Sci Adv, 8, eabg9215, 10.1126/sciadv.abg9215 · DOI
- 10.1038/nature22799 · DOI
- 10.7554/eLife.06380 · DOI
- 10.1016/j.cell.2016.11.020 · DOI
- Punjani, A. and D.J. Fleet , 3D Flexible Refinement: Structure and Motion of Flexible Proteins from Cryo-EM. bioRxiv, 2021: p. 2021.04.22.440893. · DOI
- 10.1002/PRO.3943 · DOI
Metadata
- Authors
- Afonine, P. V., Gobet, A., Moissonnier, L., Poon, B. K., & Chaptal, V.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- Centre National de la Recherche Scientifique (FR)
- Lyon 1 Université (FR)
- Corresponding author
- Afonine, Pavel V.
- Chaptal, Vincent
- Venue
- Biochimica et Biophysica Acta (BBA) - Biomembranes
- Publisher
- openRxiv
- Published
- 2022-12-23
- Volume
- 1865
- Issue
- 4
- Pages
- 184133-184133
- ISSN
- 0005-2736 (ISSN-L)
- OpenAlex
- W4318943895
- Cited by
- 18
- References
- 1
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 4 · 2023: 3
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochimica et Biophysica Acta (BBA) - Biomembranes (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- U.S. Department of Energy (-AC02-05CH11231, 05CH11231, DE AC02 05CH11231, DE-AC02-)
- Agence Nationale de la Recherche (ANR‐19, DE-AC02-05CH11231, ANR-19-CE11-0023)
- Centre National de la Recherche Scientifique (DE-AC02-05CH11231)
- National Institutes of Health (DE-AC02–05CH11231)
- College of Natural Resources and Sciences, Humboldt State University
- National Institute of General Medical Sciences (P01GM063210, R01GM071939, R24GM141254)
- 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
- cryo-electron microscopy, conformational heterogeneity, ensemble refinement, protein motion, sample heterogeneity, molecular dynamics comparison, ligand flexibility
- MeSH terms
- Protein Conformation, Proteins, Software, Cryoelectron Microscopy, Molecular Dynamics Simulation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
