Local defocus estimation in single particle analysis in cryo-electron microscopy

Single Particle analysis (SPA) aims to determine the three-dimensional structure of proteins and macromolecular complexes. The current state of the art has allowed us to achieve near-atomic and even atomic resolutions. To obtain high-resolution structures, a set of well-defined image processing step...

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Detalles Bibliográficos
Autores: Fernández-Giménez, Elena, Carazo, José M., Sorzano, Carlos Óscar S.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/363522
Acceso en línea:http://hdl.handle.net/10261/363522
https://api.elsevier.com/content/abstract/scopus_id/85173002101
Access Level:acceso abierto
Palabra clave:CTF
Cryo-EM
Defocus
High-resolution
Local defocus
SPA
Descripción
Sumario:Single Particle analysis (SPA) aims to determine the three-dimensional structure of proteins and macromolecular complexes. The current state of the art has allowed us to achieve near-atomic and even atomic resolutions. To obtain high-resolution structures, a set of well-defined image processing steps is required. A critical one is the estimation of the Contrast Transfer Function (CTF), which considers the sample defocus and aberrations of the microscope. Defocus is usually globally estimated; in this case, it is the same for all the particles in each micrograph. But proteins are ice-embedded at different heights, suggesting that defocus should be measured in a local (per particle) manner. There are four state-of-the-art programs to estimate local defocus (Gctf, Relion, CryoSPARC, and Xmipp). In this work, we have compared the results of these software packages to check whether the resolution improves. We have used the Scipion framework and developed a specific program to analyze local defocus. The results produced by different programs do not show a clear consensus using the current test datasets in this study.