A Theoretical Study of the Physicochemical Mechanisms Associated with DNA Recognition Modulation in Artificial Zinc-Finger Proteins
| Autor: | Hirotoshi Mori, Kaori Ueno-Noto |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Stereochemistry
Molecular Sequence Data Mutant Ab initio Molecular Dynamics Simulation Protein Structure Secondary chemistry.chemical_compound Molecular dynamics Materials Chemistry Amino Acid Sequence Physical and Theoretical Chemistry Zinc finger chemistry.chemical_classification Zinc Fingers DNA Surfaces Coatings and Films Amino acid DNA-Binding Proteins Models Chemical chemistry Modulation Mutation Thermodynamics Fragment molecular orbital Protein Binding |
| Zdroj: | The Journal of Physical Chemistry B. 115:4774-4780 |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/jp1097348 |
| Popis: | The DNA-binding ability of the zinc-finger (ZF) protein and the modulation of its affinity to DNA through amino acid mutations were theoretically investigated. Classical molecular dynamics and energy decomposition analysis based on large-scale ab initio fragment molecular orbital calculations were used to obtain the DNA binding affinities of wild-type and three mutant ZFs. Calculated binding free energies qualitatively well explained the DNA binding affinity modulation experimentally observed by Dhanasekaran et al. [Dhanasekaran, M.; et al., Biochemistry 2007, 46, 7506-7513]. It had been considered that only the α-helix domain in the ZF plays an important role in DNA recognition; however, our results clearly show that the N-terminal regions, BR1 and BR2, also play important roles in DNA recognition. |
| Databáze: | OpenAIRE |
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