Propagation of Conformational Coordinates Across Angular Space in Mapping the Continuum of States from Cryo-EM Data by Manifold Embedding
Year: 2023
Type: book-chapter
Abstract: Recent approaches to the study of biological molecules employ manifold learning to single-particle cryogenic electron microscopy data sets to map the continuum of states of a molecule into a low-dimensional space spanned by eigenvectors or “conformational coordinates.” This chapter presents an approach to automate the propagation of conformational coordinates across all projection directions (PDs), in contrast to the current manual-selection approach, which entails user inspection of the movies for each PD and visual comparison of movies in adjacent PDs. The propagation process is formulated as an optimization problem, where the “closeness” of the conformational changes in the movies is maximized. The chapter utilizes a feature-extraction technique to encode the conformational change and then employ graphical models to propagate this information across angular space. A manifold embedding-based technique recently introduced enables the quantitative study of continuous conformational motions over the energy landscape.
Authors: Suvrajit Maji, Hstau Liao, Ali Dashti, Ghoncheh Mashayekhi, Abbas Ourmazd, Joachim Frank
Institutions: Columbia University, University of Wisconsin–Milwaukee
Language: English
Subfield: Structural Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4385345650