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https://hdl.handle.net/20.500.14094/90005500
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2024-10-05
21:54 集計
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90005500 (fulltext)
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2.09 MB
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メタデータID
90005500
アクセス権
open access
出版タイプ
Version of Record
タイトル
Towards good correlation between fragment molecular orbital interaction energies and experimental IC50 for ligand binding: A case study of p38 MAP kinase
著者
Sheng, Yinglei ; Watanabe, Hirofumi ; Maruyama, Keiya ; Watanabe, Chiduru ; Okiyama, Yoshio ; Honma, Teruki ; Fukuzawa, Kaori ; Tanaka, Shigenori
著者名
Sheng, Yinglei
著者ID
A1322
著者名
Watanabe, Hirofumi
渡邉, 博文
ワタナベ, ヒロフミ
所属機関名
学術研究推進機構
著者名
Maruyama, Keiya
著者名
Watanabe, Chiduru
著者名
Okiyama, Yoshio
著者名
Honma, Teruki
著者名
Fukuzawa, Kaori
著者ID
A0271
研究者ID
1000010379480
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=c07e328da483e766520e17560c007669
著者名
Tanaka, Shigenori
田中, 成典
タナカ, シゲノリ
所属機関名
システム情報学研究科
言語
English (英語)
収録物名
Computational and Structural Biotechnology Journal
巻(号)
16
ページ
421-434
出版者
Elsevier B.V.
刊行日
2018
公開日
2019-01-16
抄録
We describe several procedures for the preprocessing of fragment molecular orbital (FMO) calculations on p38 mitogen-activated protein (MAP) kinase and discuss the influence of the procedures on the protein-ligand interaction energies represented by inter-fragment interaction energies (IFIEs). The correlation between the summation of IFIEs for a ligand and amino acid residues of protein (IFIE-sum) and experimental affinity values (IC50) was poor when considered for the whole set of protein-ligand complexes. To improve the correlation for prediction of ligand binding affinity, we carefully classified data set by the ligand charge, the DFG-loop state (DFG-in/out loop), which is characteristic of kinase, and the scaffold of ligand. The correlation between IFIE-sums and the activity values was examined using the classified data set. As a result, it was confirmed that there was a selected data set that showed good correlation between IFIE-sum and activity value by appropriate classification. In addition, we found that the differences in protonation and hydrogen orientation caused by subtle differences in preprocessing led to a relatively large difference in IFIE values. Further, we also examined the effect of structure optimization with different force fields. It was confirmed that the difference in the force field had no significant effect on IFIE-sum. From the viewpoint of drug design using FMO calculations, various investigations on IFIE-sum in this research, such as those regarding several classifications of data set and the different procedures of structural preparation, would be expected to provide useful knowledge for improvement of prediction ability about the ligand binding affinity.
キーワード
Ab initio calculation
FMO method
p38 MAP kinase
Ligand binding affinity
In silico screening
カテゴリ
システム情報学研究科
学術研究推進機構
学術雑誌論文
権利
© 2018 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
関連情報
DOI
https://doi.org/10.1016/j.csbj.2018.10.003
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資源タイプ
journal article
eISSN
2001-0370
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