Accurate model and ensemble refinement using cryo-electron microscopy maps and Bayesian inference.

Autor: Samuel E Hoff, F Emil Thomasen, Kresten Lindorff-Larsen, Massimiliano Bonomi
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: PLoS Computational Biology, Vol 20, Iss 7, p e1012180 (2024)
Druh dokumentu: article
ISSN: 1553-734X
1553-7358
DOI: 10.1371/journal.pcbi.1012180
Popis: Converting cryo-electron microscopy (cryo-EM) data into high-quality structural models is a challenging problem of outstanding importance. Current refinement methods often generate unbalanced models in which physico-chemical quality is sacrificed for excellent fit to the data. Furthermore, these techniques struggle to represent the conformational heterogeneity averaged out in low-resolution regions of density maps. Here we introduce EMMIVox, a Bayesian inference approach to determine single-structure models as well as structural ensembles from cryo-EM maps. EMMIVox automatically balances experimental information with accurate physico-chemical models of the system and the surrounding environment, including waters, lipids, and ions. Explicit treatment of data correlation and noise as well as inference of accurate B-factors enable determination of structural models and ensembles with both excellent fit to the data and high stereochemical quality, thus outperforming state-of-the-art refinement techniques. EMMIVox represents a flexible approach to determine high-quality structural models that will contribute to advancing our understanding of the molecular mechanisms underlying biological functions.
Databáze: Directory of Open Access Journals
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