ArticleProceedings of the National Academy of Sciences of the United States of America2008
Urea denaturation by stronger dispersion interactions with proteins than water implies a 2-stage unfolding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.
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139 citing papers in PubMed, 536 citations in OpenAlex.
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- Comparison of Sucrose and Trehalose for Protein Stabilization Using Differential Scanning Calorimetry.The journal of physical chemistry. B · 2024Article
- Trimethylamine-N-oxide depletes urea in a peptide solvation shell.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Isothermal chemical denaturation assay for monitoring protein stability and inhibitor interactions.Scientific reports · 2023Article
79 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The mechanism of denaturation of proteins by urea is explored by using all-atom microseconds molecular dynamics simulations of hen lysozyme generated on BlueGene/L. Accumulation of urea around lysozyme shows that water molecules are expelled from the first hydration shell of the protein. We observe a 2-stage penetration of the protein, with urea penetrating the hydrophobic core before water, forming a "dry globule." The direct dispersion interaction between urea and the protein backbone and side chains is stronger than for water, which gives rise to the intrusion of urea into the protein interior and to urea's preferential binding to all regions of the protein. This is augmented by preferential hydrogen bond formation between the urea carbonyl and the backbone amides that contributes to the breaking of intrabackbone hydrogen bonds. Our study supports the "direct interaction mechanism" whereby urea has a stronger dispersion interaction with protein than water.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.