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Computational Prediction of the Mode of Binding of Antitumor Lankacidin C to Tubulin
https://hiroshima.repo.nii.ac.jp/records/2006141
https://hiroshima.repo.nii.ac.jp/records/2006141dbe8e783-de8a-44c6-a0f4-a13fab849854
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
ACSOmega_4_4461.pdf (6.4 MB)
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| Item type | デフォルトアイテムタイプ_（フル）(1) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 公開日 | 2023-03-18 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Computational Prediction of the Mode of Binding of Antitumor Lankacidin C to Tubulin | |||||||||||
| 言語 | en | |||||||||||
| 作成者 |
Ayoub, Ahmed Taha
× Ayoub, Ahmed Taha
× Elrefaiy, Mohamed Ali
× Arakawa, Kenji
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| アクセス権 | ||||||||||||
| アクセス権 | open access | |||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||
| 権利情報 | ||||||||||||
| 権利情報 | © 2019 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述 | Lankacidin C, which is an antibiotic produced by the organism Streptomyces rochei, shows considerable antitumor activity. The mechanism of its antitumor activity remained elusive for decades until it was recently shown to overstabilize microtubules by binding at the taxol binding site of tubulin, causing mitotic arrest followed by apoptosis. However, the exact binding mode of lankacidin C inside the tubulin binding pocket remains unknown, an issue that impedes proper structure-based design, modification, and optimization of the drug. Here, we have used computational methods to predict the most likely binding mode of lankacidin C to tubulin. We employed ensemble-based docking in different software packages, supplemented with molecular dynamics simulation and subsequent binding-energy prediction. The molecular dynamics simulations performed on lankacidin C were collectively 1.1 μs long. Also, a multiple-trajectory approach was performed to assess the stability of different potential binding modes. The identified binding mode could serve as an ideal starting point for structural modification and optimization of lankacidin C to enhance its affinity to the tubulin binding site and therefore improve its antitumor activity. | |||||||||||
| 言語 | en | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.8b03470. | |||||||||||
| 出版者 | ||||||||||||
| 出版者 | American Chemical Society | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| 資源タイプ | ||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||||||
| 資源タイプ | journal article | |||||||||||
| 出版タイプ | ||||||||||||
| 出版タイプ | VoR | |||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
| 関連情報 | ||||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | 10.1021/acsomega.8b03470 | |||||||||||
| 関連情報 | ||||||||||||
| 識別子タイプ | PMID | |||||||||||
| 関連識別子 | 31459641 | |||||||||||
| 関連情報 | ||||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | https://doi.org/10.1021/acsomega.8b03470 | |||||||||||
| 収録物識別子 | ||||||||||||
| 収録物識別子タイプ | ISSN | |||||||||||
| 収録物識別子 | 2470-1343 | |||||||||||
| 開始ページ | ||||||||||||
| 開始ページ | 4461 | |||||||||||
| 書誌情報 |
ACS Omega ACS Omega 巻 4, 号 2, p. 4461-4471, 発行日 2019-02-28 |
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| 旧ID | 48673 | |||||||||||
