Complex water networks visualized by cryogenic electron microscopy of RNA

Rachael C. Kretsch, Shanshan Li, Grigore Pintilie, Michael Z. Palo, David A. Case, Rhiju Das (), Kaiming Zhang () and Wah Chiu ()
Additional contact information
Rachael C. Kretsch: Stanford University School of Medicine
Shanshan Li: University of Science and Technology of China
Grigore Pintilie: Stanford University School of Medicine
Michael Z. Palo: Stanford University School of Medicine
David A. Case: Rutgers University
Rhiju Das: Stanford University School of Medicine
Kaiming Zhang: University of Science and Technology of China
Wah Chiu: Stanford University School of Medicine

Nature, 2025, vol. 642, issue 8066, 250-259

Abstract: Abstract The stability and function of biomolecules are directly influenced by their myriad interactions with water1–16. Here we investigated water through cryogenic electron microscopy (cryo-EM) on a highly solvated molecule: the Tetrahymena ribozyme. By using segmentation-guided water and ion modelling (SWIM)17,18, an approach combining resolvability and chemical parameters, we automatically modelled and cross-validated water molecules and Mg2+ ions in the ribozyme core, revealing the extensive involvement of water in mediating RNA non-canonical interactions. Unexpectedly, in regions where SWIM does not model ordered water, we observed highly similar densities in both cryo-EM maps. In many of these regions, the cryo-EM densities superimpose with complex water networks predicted by molecular dynamics, supporting their assignment as water and suggesting a biophysical explanation for their elusiveness to conventional atomic coordinate modelling. Our study demonstrates an approach to unveil both rigid and flexible waters that surround biomolecules through cryo-EM map densities, statistical and chemical metrics, and molecular dynamics simulations.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-025-08855-w Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:642:y:2025:i:8066:d:10.1038_s41586-025-08855-w

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-025-08855-w

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().