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

This article presents an original approach for extracting atomic-resolution landscapes of continuous con-formational 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 dynam-ics (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.(c) 2023 Elsevier Ltd. All rights reserved.

Automated summary

This article presents a new method for extracting atomic-resolution landscapes of continuous conformational variability of biomolecular complexes from cryo-EM single particle images. The method, called MDSPACE, uses a 3D-to-2D flexible fitting method based on molecular dynamics simulation and is embedded in an iterative conformational-landscape refinement scheme. The article describes the MDSPACE approach and demonstrates its performance using synthetic and experimental datasets.