RT Journal Article
SR Electronic
T1 Ensemble Refinement of mismodeled cryo-EM RNA Structures Using All-Atom Simulations
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2024.07.24.604258
DO 10.1101/2024.07.24.604258
A1 Posani, Elisa
A1 Janoš, Pavel
A1 Haack, Daniel
A1 Toor, Navtej
A1 Bonomi, Massimiliano
A1 Magistrato, Alessandra
A1 Bussi, Giovanni
YR 2024
UL http://biorxiv.org/content/early/2024/09/18/2024.07.24.604258.abstract
AB The advent of single-particle cryogenic electron microscopy (cryo-EM) has enabled near-atomic resolution imaging of large macromolecules, enhancing functional insights. However, current cryo-EM refinement tools condense all single-particle images into a single structure, which can misrepresent highly flexible molecules like RNAs. Here, we combine molecular dynamics simulations with cryo-EM density maps to better account for the structural dynamics of a complex and biologically relevant RNA macromolecule. Namely, using metainference, a Bayesian method, we reconstruct an ensemble of structures of the group II intron ribozyme, which better match experimental data, and we reveal inaccuracies of single-structure approaches in modeling flexible regions. An analysis of all RNA-containing structures deposited in the PDB reveal that this issue affects most cryo-EM structures in the 2.5—4 Å range. Thus, RNA structures determined by cryo-EM require careful handling, and our method may be broadly applicable to other RNA systems.Competing Interest StatementThe authors have declared no competing interest.