Coherent Microscopic Picture for Urea-Induced Denaturation of Proteins
| Autor: | Zaixing Yang, Peng Xiu, Ruhong Zhou, Lan Hua, Biyun Shi |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
chemistry.chemical_classification
Protein Denaturation Aqueous solution Static Electricity Proteins Hydrogen Bonding Peptide Preferential binding Molecular Dynamics Simulation Surfaces Coatings and Films Molecular dynamics chemistry.chemical_compound chemistry Biochemistry Materials Chemistry Urea Side chain Animals Muramidase Denaturation (biochemistry) Physical and Theoretical Chemistry Lysozyme Chickens |
| Zdroj: | The Journal of Physical Chemistry B. 116:8856-8862 |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/jp304114h |
| Popis: | In a previous study, we explored the mechanism of urea-induced denaturation of proteins by performing molecular dynamics (MD) simulations of hen lysozyme in 8 M urea and supported the "direct interaction mechanism" whereby urea denatures protein via dispersion interaction (Hua, L.; Zhou, R. H.; Thirumalai, D.; Berne, B. J. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 16928). Here we perform large scale MD simulations of five representative protein/peptide systems in aqueous urea to investigate if the above mechanism is common to other proteins. In all cases, accumulations of urea around proteins/peptide are observed, suggesting that urea denatures proteins by directly attacking protein backbones and side chains rather than indirectly disrupting water structure as a "water breaker". Consistent with our previous case study of lysozyme, the current energetic analyses with five protein/peptide systems reveal that urea's preferential binding to proteins mainly comes from urea's stronger dispersion interactions with proteins than with bulk solution, whereas the electrostatic (hydrogen-bonded) interactions only play a relatively minor (even negative) role during this denaturation process. Furthermore, the simulations of the peptide system at different urea concentrations (8 and 4.5 M), and with different force fields (CHARMM and OPLSAA) suggest that the above mechanism is robust, independent of the urea concentration and force field used. Last, we emphasize the importance of periodic boundary conditions in pairwise energetic analyses. This article provides a comprehensive study on the physical mechanism of urea-induced protein denaturation and suggests that the "dispersion-interaction-driven" mechanism should be general. |
| Databáze: | OpenAIRE |
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