MDSPACE: Extracting Continuous Conformational Landscapes from Cryo-EM Single Particle Datasets Using 3D-to-2D Flexible Fitting based on Molecular Dynamics Simulation

[Display omitted] •MDSPACE extracts continuous conformational landscapes from single particle datasets.•It uses MD-simulation-based 3D-to-2D flexible fitting of an atomic structure to images.•It refines conformational landscapes using principal motion directions learned iteratively.•Its performance...

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Bibliographic Details
Published in:Journal of molecular biology Vol. 435; no. 9; p. 167951
Main Authors: Vuillemot, Rémi, Mirzaei, Alex, Harastani, Mohamad, Hamitouche, Ilyes, Fréchin, Léo, Klaholz, Bruno P., Miyashita, Osamu, Tama, Florence, Rouiller, Isabelle, Jonic, Slavica
Format: Journal Article
Language:English
Published: Netherlands Elsevier Ltd 01.05.2023
Elsevier
Subjects:
3D-to-2D flexible fitting
Biochemistry, Molecular Biology
Bioinformatics
Biophysics
Computer Science
conformational landscapes
continuous conformational variability
cryo electron microscopy (cryo-EM)
Cryoelectron Microscopy - methods
Image Processing
Life Sciences
Machine Learning
Modeling and Simulation
Molecular biology
Molecular Dynamics Simulation
molecular dynamics simulation (MD simulation)
Protein Conformation
Single Molecule Imaging
Software Engineering
Structural Biology
cryo electron microscopy (cryo-EM)
3D-to-2D flexible fitting
molecular dynamics simulation (MD simulation)
continuous conformational variability
conformational landscapes
Cryo electron microscopy (cryo-EM)
single particle analysis
principal component analysis
ISSN:0022-2836, 1089-8638, 1089-8638
Online Access:Get full text
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Summary:[Display omitted] •MDSPACE extracts continuous conformational landscapes from single particle datasets.•It uses MD-simulation-based 3D-to-2D flexible fitting of an atomic structure to images.•It refines conformational landscapes using principal motion directions learned iteratively.•Its performance is shown with synthetic and experimental data. This article presents an original approach for extracting atomic-resolution landscapes of continuous conformational variability of biomolecular complexes from cryo electron microscopy (cryo-EM) single particle images. This approach is based on a new 3D-to-2D flexible fitting method, which uses molecular dynamics (MD) simulation and is embedded in an iterative conformational-landscape refinement scheme. This new approach is referred to as MDSPACE, which stands for Molecular Dynamics simulation for Single Particle Analysis of Continuous Conformational hEterogeneity. The article describes the MDSPACE approach and shows its performance using synthetic and experimental datasets.
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ISSN:0022-2836
1089-8638
1089-8638
DOI:10.1016/j.jmb.2023.167951