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Geometric Shape Matching for Recovering Protein Conformations from Single-Particle Cryo-EM Data
Department of mathematical sciences, Chalmers University of Technology and Gothenburg University, Gothen-burg, Sweden.
KTH, School of Engineering Sciences (SCI), Mathematics (Dept.), Numerical Analysis, Optimization and Systems Theory.
Department of mathematical sciences, Chalmers University of Technology and Gothenburg University, Gothen-burg, Sweden.
KTH, School of Engineering Sciences (SCI), Mathematics (Dept.), Numerical Analysis, Optimization and Systems Theory.ORCID iD: 0000-0002-1118-6483
2025 (English)In: SIAM Journal on Imaging Sciences, E-ISSN 1936-4954, Vol. 18, no 4, p. 2509-2546Article in journal (Refereed) Published
Abstract [en]

We address recovery of the three-dimensional backbone structure of single polypeptide proteins from single-particle cryo--electron microscopy (Cryo-SPA) data. Cryo-SPA produces noisy tomographic projections of electrostatic potentials of macromolecules. From these projections, we use methods from shape analysis to recover the three-dimensional backbone structure. Thus, we view the reconstruction problem as an indirect matching problem, where a point cloud representation of the protein backbone is deformed to match two-dimensional tomography data. The deformations are obtained via the action of a matrix Lie group. By selecting a deformation energy, the optimality conditions are obtained, which lead to computational algorithms for optimal deformations. We showcase our approach on synthetic data, for which we recover the three-dimensional structure of the backbone.

Place, publisher, year, edition, pages
Society for Industrial & Applied Mathematics (SIAM) , 2025. Vol. 18, no 4, p. 2509-2546
Keywords [en]
cryogenic electron microscopy, electron microscopy, inverse problems, Lie groups, manifold-valued data, optimization, regularization, shape analysis, single particle analysis, tomography
National Category
Biophysics Computational Mathematics
Identifiers
URN: urn:nbn:se:kth:diva-375706DOI: 10.1137/24M1704336ISI: 001620567600008Scopus ID: 2-s2.0-105026339801OAI: oai:DiVA.org:kth-375706DiVA, id: diva2:2029716
Note

QC 20260119

Available from: 2026-01-19 Created: 2026-01-19 Last updated: 2026-01-19Bibliographically approved

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Krook, JonathanÖktem, Ozan

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