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

PLoS Comput Biol

Institut Pasteur, Université Paris Cité, CNRS UMR 3528, Computational Structural Biology Unit, Paris, France.

Published: July 2024

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271924PMC
http://dx.doi.org/10.1371/journal.pcbi.1012180DOI Listing

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