2024Hoff EMMIVox

Citation

Hoff, Samuel E. / Thomasen, F. Emil / Lindorff-Larsen, Kresten / Bonomi, Massimiliano. Accurate model and ensemble refinement using cryo-electron microscopy maps and Bayesian inference. 2024. PLOS Computational Biology, Vol. 20, No. 7, p. e1012180

Abstract

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 stateof- 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.

Links

https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1012180