2022/09/29 by Youssef S. G. Nashed, Ariana Peck, Nashed, Youssef +15 · 2 citations
Biochemistry, Genetics and Molecular Biology · Materials Science · Physics and Astronomy · #Advanced Electron Microscopy Techniques and Applications #Biomolecules (q-bio.BM) #Chemical Physics (physics.chem-ph) #Computer Vision and Pattern Recognition (cs.CV) #Electron and X-Ray Spectroscopy Techniques #FOS: Biological sciences #FOS: Computer and information sciences #FOS: Electrical engineering #FOS: Physical sciences #Force Microscopy Techniques and Applications #Image and Video Processing (eess.IV) #electronic engineering #information engineering
paper · pdf · doi:10.48550/arxiv.2209.15121
openalex publication_date 2022/09/29 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Cryogenic electron microscopy (cryo-EM) provides a unique opportunity to study the structural heterogeneity of biomolecules. Being able to explain this heterogeneity with atomic models would help our understanding of their functional mechanisms but the size and ruggedness of the structural space (the space of atomic 3D cartesian coordinates) presents an immense challenge. Here, we describe a heterogeneous reconstruction method based on an atomistic representation whose deformation is reduced to a handful of collective motions through normal mode analysis. Our implementation uses an autoencoder. The encoder jointly estimates the amplitude of motion along the normal modes and the 2D shift between the center of the image and the center of the molecule . The physics-based decoder aggregates a representation of the heterogeneity readily interpretable at the atomic level. We illustrate our method on 3 synthetic datasets corresponding to different distributions along a simulated trajectory of adenylate kinase transitioning from its open to its closed structures. We show for each distribution that our approach is able to recapitulate the intermediate atomic models with atomic-level accuracy.