Bayesian inference of initial models in cryo-electron microscopy using pseudo-atoms

Biophysical Journal
Paul Joubert, Michael Habeck

Abstract

Single-particle cryo-electron microscopy is widely used to study the structure of macromolecular assemblies. Tens of thousands of noisy two-dimensional images of the macromolecular assembly viewed from different directions are used to infer its three-dimensional structure. The first step is to estimate a low-resolution initial model and initial image orientations. This is a challenging global optimization problem with many unknowns, including an unknown orientation for each two-dimensional image. Obtaining a good initial model is crucial for the success of the subsequent refinement step. We introduce a probabilistic algorithm for estimating an initial model. The algorithm is fast, has very few algorithmic parameters, and yields information about the precision of estimated model parameters in addition to the parameters themselves. Our algorithm uses a pseudo-atomic model to represent the low-resolution three-dimensional structure, with isotropic Gaussian components as moveable pseudo-atoms. This leads to a significant reduction in the number of parameters needed to represent the three-dimensional structure, and a simplified way of computing two-dimensional projections. It also contributes to the speed of the algorithm. We combin...Continue Reading

References

Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Oct 13, 2004·Journal of Structural Biology·C O S SorzanoA Pascual-Montano
Apr 6, 2005·Journal of Molecular Biology·Sjors H W ScheresJose-Maria Carazo
Jul 25, 2006·Journal of Structural Biology·Guang TangSteven J Ludtke
Sep 19, 2006·Journal of Structural Biology·Xiaodong YanTimothy S Baker
Dec 21, 2006·Nature Methods·Sjors H W ScheresJose-Maria Carazo
Nov 22, 2011·Journal of Molecular Biology·Sjors H W Scheres
Jun 1, 1984·IEEE Transactions on Pattern Analysis and Machine Intelligence·S Geman, D Geman
Jul 31, 2012·Nature Methods·Sjors H W Scheres, Shaoxia Chen
Aug 21, 2012·Journal of Structural Biology·Dominika Elmlund, Hans Elmlund
Sep 25, 2012·Journal of Structural Biology·Sjors H W Scheres
May 15, 2013·Nucleic Acids Research·R Nogales-CadenasC O S Sorzano
Mar 19, 2014·Journal of Structural Biology·Zhizhen Zhao, Amit Singer

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Citations

Aug 18, 2017·PloS One·Yi-Ling Chen, Michael Habeck
Jun 8, 2021·Frontiers in Molecular Biosciences·Nima Vakili, Michael Habeck

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