ArticleProceedings of the National Academy of Sciences of the United States of America2011
Accessing protein conformational ensembles using room-temperature X-ray crystallography.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 375 papers.
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Who cites it
375 citing papers in PubMed.
- Exploring the bistable equilibrium of methylated CpG DNA recognition by the MBD2 protein.Nucleic acids research · 2026Article
- 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
- Review
- Aromatic ring flips reveal reshaping of protein dynamics in crystals and complexes.Nature chemistry · 2026Article
- Target identification and assessment in the era of AI.Nature reviews. Drug discovery · 2026Review
- Understanding how enzymes work: the journey to ensemble-function studies.The FEBS journal · 2026Review
- CAGE-TRX expands the scope of time-resolved crystallography through genetically encoded active-site photocaging.bioRxiv : the preprint server for biology · 2026Article
- Pinpointing Protein Crystal Structures over a Broad Temperature Range Using Hydrophobic Protection.ACS omega · 2026Article
- From possibility to precision in macromolecular ensemble prediction.Nature methods · 2026Review
- Structural insights into urocanate reductase using room-temperature X-ray crystallography.Acta crystallographica. Section D, Structural biology · 2026Article
- Thermodynamic prediction of RNA cellular activity from sequence via conformational ensembles.Cell · 2026Article
- A Risk-Tiered Validation Framework for Artificial Intelligence in Drug Discovery: From Reproducibility to Clinical Translation.International journal of molecular sciences · 2026Review
- An integrated experimental and computational pipeline for crystallographic fragment screening of membrane protein in the lipid cubic phase.Communications chemistry · 2026Article
- Temperature-Dependent Conformational Dynamics of Substrate Entrance Loops in β-Glucosidase: Insights from Molecular Dynamics Simulations.International journal of molecular sciences · 2026Article
- Structural basis for substrate-dependent allostery in oxygen activation by a cytochrome P450 enzyme revealed by analysis at different temperatures.Chemical science · 2026Article
- High-throughput biochemical phenotyping of SHP2 variants reveals the molecular basis of diseases and allosteric drug inhibition.bioRxiv : the preprint server for biology · 2026Article
- Coupled on-line in crystallo UV-Vis absorption spectroscopy and X-ray crystallography to compare specific radiation damage in metal-containing proteins at room versus cryogenic temperature.Acta crystallographica. Section D, Structural biology · 2026Article
- Unfreezing structural biology for drug discovery.Nature chemical biology · 2026Review
- Decrypting cryptic pockets with physics-based simulations and artificial intelligence.Current opinion in structural biology · 2026Review
- Some Like It Hot -Structural Changes in Extremophile Rubredoxin at 120 °C.Angewandte Chemie (International ed. in English) · 2026Article
315 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
Abstract
Modern protein crystal structures are based nearly exclusively on X-ray data collected at cryogenic temperatures (generally 100 K). The cooling process is thought to introduce little bias in the functional interpretation of structural results, because cryogenic temperatures minimally perturb the overall protein backbone fold. In contrast, here we show that flash cooling biases previously hidden structural ensembles in protein crystals. By analyzing available data for 30 different proteins using new computational tools for electron-density sampling, model refinement, and molecular packing analysis, we found that crystal cryocooling remodels the conformational distributions of more than 35% of side chains and eliminates packing defects necessary for functional motions. In the signaling switch protein, H-Ras, an allosteric network consistent with fluctuations detected in solution by NMR was uncovered in the room-temperature, but not the cryogenic, electron-density maps. These results expose a bias in structural databases toward smaller, overpacked, and unrealistically unique models. Monitoring room-temperature conformational ensembles by X-ray crystallography can reveal motions crucial for catalysis, ligand binding, and allosteric regulation.
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