2023Esteve Spectral

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Esteve-Yagüe, Carlos / Diepeveen, Willem / Öktem, Ozan / Schönlieb, Carola-Bibiane Spectral decomposition of atomic structures in heterogeneous cryo-EM. 2023. Inverse Problems, Vol. 39, p. 034003


We consider the problem of recovering the three-dimensional atomic structure of a exible macromolecule from a heterogeneous cryo-EM dataset. The dataset contains noisy tomographic projections of the electrostatic potential of the macromolecule, taken from dierent viewing directions, and in the heterogeneous case, each image corresponds to a dierent conformation of the macromolecule. Under the assumption that the macromolecule can be modelled as a chain, or discrete curve (as it is for instance the case for a protein backbone with a single chain of amino-acids), we introduce a method to estimate the deformation of the atomic model with respect to a given conformation, which is assumed to be known a priori. Our method consists on estimating the torsion and bond angles of the atomic model in each conformation as a linear combination of the eigenfunctions of the Laplace operator in the manifold of conformations. These eigenfunctions can be approximated by means of a well-known technique in manifold learning, based on the construction of a graph Laplacian using the cryo-EM dataset. Finally, we test our approach with synthetic datasets, for which we recover the atomic model of two-dimensional and three-dimensional exible structures from noisy tomographic projections.




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