Chris Lapointe (@lapointelab.bsky.social)

Complex water networks visualized by cryogenic electron microscopy of RNA | Nature The stability and function of biomolecules are directly influenced by their myriad interactions with water1–16. In this study, we investigated water through cryogenic electron microscopy (cryo-EM) on a highly solvated molecule, the Tetrahymena ribozyme, determined at 2.2 and 2.3 Å resolutions. By employing segmentation-guided water and ion modeling (SWIM)17,18, an approach combining resolvability and chemical parameters, we automatically modeled 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 (MD), supporting their assignment as water and suggesting a biophysical explanation for their elusiveness to conventional atomic coordinate mod https://doi.org/10.1038/s41586-025-08855-w