ArticleAngewandte Chemie (International ed. in English)2022
Water Networks Repopulate Protein-Ligand Interfaces with Temperature.
Article in Angewandte Chemie (International ed. in English), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Putrescine-bound structure and multi-temperature crystallography provide new insights into ligand binding and conformational heterogeneity in spermidine synthase.Structural dynamics (Melville, N.Y.) · 2026Article
- Unfreezing structural biology for drug discovery.Nature chemical biology · 2026Review
- WatCon: A Python Tool for Analysis of Conserved Water Networks Across Protein Families.JACS Au · 2025Article
- Multi-Temperature Crystallography of S-Adenosylmethionine Decarboxylase Observes Dynamic Loop Motions.Biomolecules · 2025Article
- Evolution of macromolecular crystallography beamlines at the Swiss Light Source and SwissFEL.Journal of synchrotron radiation · 2025Article
- Probing the modulation of enzyme kinetics by multi-temperature, time-resolved serial crystallography.Nature communications · 2025Article
- An experimental proxy of water displaceability for ligand discovery.Nature methods · 2025Article
- Article
- Development of Receptor Desolvation Scoring and Covalent Sampling in DOCK 6: Methods Evaluated on a RAS Test Set.Journal of chemical information and modeling · 2025Article
- Investigating the potential mechanism of bisphenols on neurodegeneration through network toxicology and molecular docking.NAM journal · 2025Article
- A structural perspective on the temperature-dependent activity of enzymes.bioRxiv : the preprint server for biology · 2024Article
- Article
- Changes in an enzyme ensemble during catalysis observed by high-resolution XFEL crystallography.Science advances · 2024Article
- Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.Lipids in health and disease · 2024Article
- High-resolution double vision of the allosteric phosphatase PTP1B.Acta crystallographica. Section F, Structural biology communications · 2024Article
- Changes in an Enzyme Ensemble During Catalysis Observed by High Resolution XFEL Crystallography.bioRxiv : the preprint server for biology · 2023Article
- Pan-HSP90 ligand binding reveals isoform-specific differences in plasticity and water networks.Protein science : a publication of the Protein Society · 2023Article
- FLEXR: automated multi-conformer model building using electron-density map sampling.Acta crystallographica. Section D, Structural biology · 2023Article
- In Silico Evaluation of the Thr58-Associated Conserved Water with KRAS Switch-II Pocket Binders.Journal of chemical information and modeling · 2023Article
- Molecular-dynamics simulation methods for macromolecular crystallography.Acta crystallographica. Section D, Structural biology · 2023Article
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5 authors.
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Abstract
High-resolution crystal structures highlight the importance of water networks in protein-ligand interactions. However, as these are typically determined at cryogenic temperature, resulting insights may be structurally precise but not biologically accurate. By collecting 10 matched room-temperature and cryogenic datasets of the biomedical target Hsp90α, we identified changes in water networks that impact protein conformations at the ligand binding interface. Water repositioning with temperature repopulates protein ensembles and ligand interactions. We introduce Flipper conformational barcodes to identify temperature-sensitive regions in electron density maps. This revealed that temperature-responsive states coincide with ligand-responsive regions and capture unique binding signatures that disappear upon cryo-cooling. Our results have implications for discovering Hsp90 selective ligands, and, more generally, for the utility of hidden protein and water conformations in drug discovery.
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