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Steric and Allosteric Effects of Fatty Acids on the Binding of Warfarin to Human Serum Albumin Revealed by Molecular Dynamics and Free Energy Calculations
https://repository.lib.tottori-u.ac.jp/records/7135
https://repository.lib.tottori-u.ac.jp/records/7135f1cb173e-f9b8-4058-b0ae-d4aebc203b5b
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
cpb59(7)_860.pdf (2.2 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2019-09-19 | |||||
| タイトル | ||||||
| タイトル | Steric and Allosteric Effects of Fatty Acids on the Binding of Warfarin to Human Serum Albumin Revealed by Molecular Dynamics and Free Energy Calculations | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題 | human serum albumin | |||||
| キーワード | ||||||
| 主題 | molecular dynamics simulation | |||||
| キーワード | ||||||
| 主題 | binding free energy | |||||
| キーワード | ||||||
| 主題 | multiple binding site | |||||
| キーワード | ||||||
| 主題 | warfarin | |||||
| キーワード | ||||||
| 主題 | fatty acid | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題 | human serum albumin | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題 | molecular dynamics simulation | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題 | binding free energy | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題 | multiple binding site | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題 | warfarin | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題 | fatty acid | |||||
| 資源タイプ | ||||||
| 資源タイプ | journal article | |||||
| 著者 |
Fujiwara, Shin-ichi
× Fujiwara, Shin-ichi× Amisaki, Takashi |
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| 著者所属（英） | ||||||
| 言語 | en | |||||
| 値 | Department of Biological Regulation, Faculty of Medicine, Tottori University | |||||
| 著者所属（英） | ||||||
| 言語 | en | |||||
| 値 | Department of Biological Regulation, Faculty of Medicine, Tottori University | |||||
| 抄録 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Human serum albumin (HSA) binds with drugs and fatty acids (FAs). This study was initiated to elucidate the relationship between the warfarin binding affinity of HSA and the positions of bound FA molecules. Molecular dynamics simulations of 11 HSA-warfarin-myristate complexes were performed. HSA-warfarin binding free energy was then calculated for each of the complexes by the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method. The results indicated that the magnitude of the binding free energy was smaller in HSA-warfarin complexes that had 4 or more myristate molecules than in complexes with no myristate molecules. The unfavorable effect on the HSA-warfarin binding affinity was caused sterically by the binding of a myristate molecule to the FA binding site closest to the warfarin binding site. On the other hand, the magnitude of HSA-warfarin binding free energy was largest when 3 myristate molecules were bound to the high-affinity sites. The strongest HSA-warfarin binding was attributable to favorable entropic contribution related to larger atomic fluctuations of the amino acid residues at the warfarin binding site. In the binding of 2 myristate molecules to the sites with the highest and second-highest affinities, allosteric modulation that enhanced electrostatic interactions between warfarin and some of the amino acid residues around the warfarin binding site was observed. This study clarified the structural and energetic properties of steric/allosteric effects of FAs on the HSA-warfarin binding affinity and illustrated the approach to analyze protein-ligand interactions in situations such that multiple ligands bind to the other sites of the protein. | |||||
| 書誌情報 |
Chemical & pharmaceutical bulletin en : Chemical & pharmaceutical bulletin 巻 59, 号 7, p. 860-867, 発行日 2011-07-01 |
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| 出版者 | ||||||
| 出版者 | The Pharmaceutical Society of Japan | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 00092363 | |||||
| 書誌レコードID | ||||||
| 収録物識別子タイプ | NCID | |||||
| 収録物識別子 | AA00602100 | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1248/cpb.59.860 | |||||
| 権利 | ||||||
| 権利情報 | © 2011 The Pharmaceutical Society of Japan | |||||
| 情報源 | ||||||
| 関連名称 | Shin-ichi Fujiwara, Takashi Amisaki.. Steric and Allosteric Effects of Fatty Acids on the Binding of Warfarin to Human Serum Albumin Revealed by Molecular Dynamics and Free Energy Calculations. Chemical & pharmaceutical bulletin. 2011, 59(7), 860-867 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.jstage.jst.go.jp/article/cpb/59/7/59_7_860/_article | |||||
| 関連名称 | https://www.jstage.jst.go.jp/article/cpb/59/7/59_7_860/_article | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
