近日，美国斯坦福大学医学院教授Wah Chiu及其研究团队揭示了RNA的低温电子显微镜显示的复杂水网络。相关论文发表在2025年3月11日出版的《自然》杂志上。

在这项研究中，研究组通过低温电子显微镜（cryo-EM）研究了水的高度溶剂化分子，四膜核酶，测定在2.2和2.3 决议。通过采用一种结合可分辨性和化学参数的分割引导水和离子模型（SWIM）17,18，该研究团队自动模拟和交叉验证了核酶核心中的水分子和Mg²⁺离子，揭示了水在介导RNA非规范相互作用中的广泛参与。出乎意料的是，在SWIM没有模拟有序水的地区，小组在两个低温电镜图中观察到高度相似的密度。在许多这些区域，低温电磁密度与分子动力学（MD）预测的复杂水网络叠加，支持它们作为水的分配，并为它们对传统原子坐标模型的适用性提出了生物物理学解释。他们的研究展示了一种通过低温电镜图密度、统计和化学指标以及MD模拟来揭示生物分子周围刚性和柔性水的方法。

据了解，生物分子的稳定性和功能直接受到它们与水的无数相互作用的影响。

附：英文原文

Title: Complex water networks visualized by cryogenic electron microscopy of RNA

Author: Kretsch, Rachael C., Li, Shanshan, Pintilie, Grigore, Palo, Michael Z., Case, David A., Das, Rhiju, Zhang, Kaiming, Chiu, Wah

Issue&Volume: 2025-03-11

Abstract: 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 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 modeling. 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 MD simulations.

DOI: 10.1038/s41586-025-08855-w

Source: https://www.nature.com/articles/s41586-025-08855-w