ArticleScientific reports2021
A Bayesian approach to extracting free-energy profiles from cryo-electron microscopy experiments.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 55 citations in OpenAlex.
- Bayesian Umbrella Quadrature Automates Free-Energy Calculations Across Diverse Molecular Systems and Processes.Journal of chemical theory and computation · 2026Article
- Digital twin of biomacromolecular thermodynamics in cryo-EM data.Communications chemistry · 2026Article
- Engineered Cas9 complexes establish an experimentally grounded benchmark for heterogeneous cryoEM reconstruction methods.bioRxiv : the preprint server for biology · 2026Article
- Comparing cryo-EM methods and molecular dynamics simulation to investigate heterogeneity in ligand-bound TRPV1.Nature communications · 2025Article
- Cryo-electron microscopy ensemble optimization using individual particles and physical constraints.bioRxiv : the preprint server for biology · 2025Article
- Topological Analysis Reveals Multiple Pathways in Molecular Dynamics.Journal of chemical theory and computation · 2025Article
- Elastic analysis bridges structure and dynamics of an AAA+ molecular motor.PLoS computational biology · 2025Article
- Amortized template matching of molecular conformations from cryoelectron microscopy images using simulation-based inference.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A new statistical metric for robust target detection in cryo-EM using 2D template matching.IUCrJ · 2025Article
- MELD in Action: Harnessing Data to Accelerate Molecular Dynamics.Journal of chemical information and modeling · 2025Review
- Transient interactions between the fuzzy coat and the cross-β core of brain-derived Aβ42 filaments.Science advances · 2025Article
- Structural basis of closed groove scrambling by a TMEM16 protein.Nature structural & molecular biology · 2024Article
- Bayesian reweighting of biomolecular structural ensembles using heterogeneous cryo-EM maps with the cryoENsemble method.Scientific reports · 2024Article
- A robust normalized local filter to estimate compositional heterogeneity directly from cryo-EM maps.Nature communications · 2023Article
- Scipion-EM-ProDy: A Graphical Interface for the ProDy Python Package within the Scipion Workflow Engine Enabling Integration of Databases, Simulations and Cryo-Electron Microscopy Image Processing.International journal of molecular sciences · 2023Article
- Novel Artificial Intelligence-Based Approaches for Ab Initio Structure Determination and Atomic Model Building for Cryo-Electron Microscopy.Micromachines · 2023Review
- Structural basis of closed groove scrambling by a TMEM16 protein.Research square · 2023Article
- MDTOMO method for continuous conformational variability analysis in cryo electron subtomograms based on molecular dynamics simulations.Scientific reports · 2023Article
- Methods for Cryo-EM Single Particle Reconstruction of Macromolecules Having Continuous Heterogeneity.Journal of molecular biology · 2023Review
- CryoEM reveals oligomeric isomers of a multienzyme complex and assembly mechanics.Journal of structural biology: X · 2023Article
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cryo-electron microscopy (cryo-EM) extracts single-particle density projections of individual biomolecules. Although cryo-EM is widely used for 3D reconstruction, due to its single-particle nature it has the potential to provide information about a biomolecule's conformational variability and underlying free-energy landscape. However, treating cryo-EM as a single-molecule technique is challenging because of the low signal-to-noise ratio (SNR) in individual particles. In this work, we propose the cryo-BIFE method (cryo-EM Bayesian Inference of Free-Energy profiles), which uses a path collective variable to extract free-energy profiles and their uncertainties from cryo-EM images. We test the framework on several synthetic systems where the imaging parameters and conditions were controlled. We found that for realistic cryo-EM environments and relevant biomolecular systems, it is possible to recover the underlying free energy, with the pose accuracy and SNR as crucial determinants. We then use the method to study the conformational transitions of a calcium-activated channel with real cryo-EM particles. Interestingly, we recover not only the most probable conformation (used to generate a high-resolution reconstruction of the calcium-bound state) but also a metastable state that corresponds to the calcium-unbound conformation. As expected for turnover transitions within the same sample, the activation barriers are on the order of [Formula: see text]. We expect our tool for extracting free-energy profiles from cryo-EM images to enable more complete characterization of the thermodynamic ensemble of biomolecules.
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