疎水相互作用を取り入れた薬物分子-タンパク質の相互作用の理論・計算解析と応用

2010 年度 研究成果報告書

• 研究課題/領域番号: 20590036
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 物理系薬学
• 研究機関: 徳島大学
• 研究代表者: 中馬 寛 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (20304545)
• 研究期間 (年度): 2008 – 2010
• キーワード: 創薬理論計算化学

研究概要

非経験的フラグメント分子軌道法を含む分子科学計算・シミュレーションを用いてリガンド・タンパク質問相互作用エネルギーを算出し、自由エネルギー変化の加成性と線形関係に基づく新しいカテゴリーの定量的構造相関解析(QSAR)法Linear Expression by Representative Energy terms (LERE)の提案・構築・検証を行った。LEREを新規定量的構造活性相関解析(LERE-QSAR)法として幾つかの阻害剤・タンパク質系へ適用し、有用性の検証を順次行い、その結果LERE-QSARが他の方法では得られない電子・原子レベルの情報を与えることを確認した。

研究成果

• [雑誌論文] Density Functional Theory Study of Hydrogen Atom Abstraction from a Series of para-Substituted Phenols : Why is the Hammett Constant Able to Represent Radical Reaction Rates? (2011)
  • 著者名/発表者名: Tatsusada Yoshida, Koji Hirozumi, Masataka Harada, Seiji Hitaoka, Hiroshi Chuman
  • 雑誌名: J.Org.Chem. in press
  • 査読あり
• [雑誌論文] Correlation Analyses on Binding Affinity of Substituted Benzenesulfonamides with Carbonic Anhydrase Using Ab Initio MO Calculations on Their Complex Structures (II) (2011)
  • 著者名/発表者名: Yohei Munei, Kazunori Shimamoto, Masataka Harada, Tatsusada Yoshida, Hiroshi Chuman
  • 雑誌名: Bioorganic & Medicinal Chemistry Letters Vol.21, No.1 ページ: 141-144
  • 査読あり
• [雑誌論文] Correlation Analyses on Binding Affinity of Sialic Acid Analogues with Influenza Virus Neuraminidase-1 Using ab Initio MO Calculations on Their Complex Structures (2010)
  • 著者名/発表者名: Seiji Hitaoka, Masataka Harada, Tatsusada Yoshida, Hiroshi Chuman
  • 雑誌名: Journal of Chemical Information and Modeling Vol.50, No.10 ページ: 1796-1805
  • 査読あり
• [雑誌論文] Correlation Analyses on Binding Affinity of Substituted Benzenesulfonamides with Carbonic Anhydrase Using ab Initio MO Calculations on Their Complex Structures (2010)
  • 著者名/発表者名: Tatsusda Yoshida, Yohei Munei, Seiji Hitaoka, Hiroshi Chuman
  • 雑誌名: Journal of Chemical Information and Modeling Vol.50, No.5 ページ: 850-860
  • 査読あり
• [雑誌論文] Assessment of Free Energy Expression in RISM Integral Equation Theory : Theoretical Prediction of Partition Coefficients Revisited (2010)
  • 著者名/発表者名: Seiichiro Ten-no, Jaewoon Jung, Hiroshi Chuman, Yukio Kawashima
  • 雑誌名: Molecular Physics Vol.108 ページ: 327-332
  • 査読あり
• [雑誌論文] Novel Quantitative Structure-Activity Studies of HIV-1 Protease Inhibitors of the Cyclic Urea Type Using Descriptors Derived from Molecular Dynamics and Molecular Orbital Calculations (2009)
  • 著者名/発表者名: Tatsusada Yoshida, Fujita, Toshio, Hiroshi Chuman
  • 雑誌名: Current Compter-Aided Drug Design Vol.5, No.1 ページ: 38-55
  • 査読あり
• [雑誌論文] Expression and Molecular Dynamics Studies on Effect of Amino Acid Substitutions at Arg344 in Human Cathepsin A on the Protein Local Conformation (2009)
  • 著者名/発表者名: Tatsusada Yoshida, Yoshito Kadota, Seiji Hitaoka, Eri Kori, Hiroshi Chuman
  • 雑誌名: BBA-Proteins Proteomics Vol.1794 ページ: 1693-1699
  • 査読あり
• [雑誌論文] Quantitative Structure-Activity Relationship for Inhibition of CYP2B6 and CYP3A4 by Azole Compounds - Comparison with Their Binding Affinity (2009)
  • 著者名/発表者名: Daisuke Itokawa, Aiko Yamauchi, Hiroshi Chuman
  • 雑誌名: QSAR Comb. Sci. Vol.28, No.6-7 ページ: 629-639
  • 査読あり
• [雑誌論文] Toward basic understanding of the partition coefficient log P and its application in QSAR (2008)
  • 著者名/発表者名: Hiroshi Chuman
  • 雑誌名: SAR and QSAR in Environmental Research Vol.19 ページ: 71-79
  • 査読あり
• [雑誌論文] QSAR Study of Cyclic Urea Type HIV-1 PR Inhibitors Using Ab Initio MO Calculation of Their Complex with HIV-1 PR (2008)
  • 著者名/発表者名: Tatsusada Yoshida, Kenji Yamagishi, Hiroshi Chuman
  • 雑誌名: QSAR & Combinatorial Science Vol.27, No.6 ページ: 694-703
  • 査読あり
• [雑誌論文] Flavonoids as Substrates and Inhibitors of Myeloperoxidase : Molecular Actions of Aglycone and Metabolites (2008)
  • 著者名/発表者名: Yuko Shiba, Takashi Kinoshita, Hiroshi Chuman, Yutaka Taketani, Eiji Takeda, Yoji Kato, Michitaka Naito, Kyuichi Kawabata, Akari Ishisaka, Junji Terao, Yoshichika Kawai
  • 雑誌名: Chemical Research in Toxicology Vol.21, No.8 ページ: 1600-1609
  • 査読あり
• [雑誌論文] Simple computational models of type I/type II cells in Fas signaling-induced apoptosis (2008)
  • 著者名/発表者名: Noriaki Okazaki, Ryoji Asano, Takashi Kinoshita, Hiroshi Chuman
  • 雑誌名: Journal of Theoretical Biology Vol.250, No.4 ページ: 621-633
  • 査読あり
• [学会発表] A Novel QSAR Procedure Using Full Ab Initio MO Calculations on Ligand-Protein Complexs : Carbonic Anhydrase with Substituted Benzenesulfonamides (2010)
  • 著者名/発表者名: Yohei Munei, Seiji Hitaoka, Kazunori Shimamoto, Tatsusada Yoshida, Hiroshi Chuman
  • 学会等名: The Second Decennial Meeting between Seoul National University and the University of Tokushima
  • 発表場所: Awaji
  • 年月日: 2010-12-23
• [学会発表] Correlation Analyses on Binding Affinity of Sialic Acid Analogues with Influenza Virus Neuraminidase-1 Using Ab Initio MO Calculations on Their Complex Structures (2010)
  • 著者名/発表者名: Seiji Hitaoka, Hiroshi Matoba, Eri Kori, Masataka Harada, Tatsusada Yoshida, Hiroshi Chuman
  • 学会等名: Asia Hub for e-Drug Discovery Symposium (AHeDD) 2010
  • 発表場所: Seoul, Korea
  • 年月日: 2010-12-18
• [学会発表] Molecular Modeling of Human Neuraminidase-1 : Structure-Activity Relation of Sialic Acid Analogs against Neuraminidases as Validation of Modeling (2010)
  • 著者名/発表者名: Seiji Hitaoka, Masataka Harada, Eri Kori, Hiroshi Matoba, Satoshi Kitao, Motiur Md.Rahman, Tatsusada Yoshida, Daisuke Tsuji, Takatsugu Hirokawa, Kouji Itou, Hiroshi Chuman
  • 学会等名: Asia Hub for e-Drug Discovery Symposium (AHeDD) 2010
  • 発表場所: Seoul, Korea
  • 年月日: 2010-12-18
• [学会発表] Toward a New Age of Quantitative Structure-Activity Relationship : Linear Expression by Representative Energy terms (2010)
  • 著者名/発表者名: Hiroshi Chuman
  • 学会等名: Asia Hub for e-Drug Discovery Symposium (AHeDD) 2010
  • 発表場所: Seoul, Korea
  • 年月日: 2010-12-18
• [学会発表] Ab initio Fragment MO Study of Complexes between Influenza Neuraminidase-1 and Various Type of Sialic Acid Analogues (2009)
  • 著者名/発表者名: Seiji Hitaoka, Eri Kori, Masataka Harada, Tatsusada Yoshida, Hiroshi Chuman
  • 学会等名: The Second French-Japanese Workshop on Computational Methods in Chemistry 2009
  • 発表場所: Nishinomiya
  • 年月日: 2009-11-28
• [学会発表] Expression and Molecular Dynamics Studies on Effect of Amino Acid Substitutions at Arg344 in Human Cathepsin A (2009)
  • 著者名/発表者名: Seiji Hitaoka, Eri Kori, Masataka Harada, Yoshito Kadota, Yasushi Horikawa, Tatsusada Yoshida, Kouji Itou, Hiroshi Chuman
  • 学会等名: The Second French-Japanese Workshop on Computational Methods in Chemistry 2009
  • 発表場所: Nishinomiya
  • 年月日: 2009-11-28
• [学会発表] QSAR Study of Cyclic Urea Type HIV-1 Protease Inhibitors Using Ab Initio Fragment MO Calculation of Their Complex Structures with HIV-1 Protease (2009)
  • 著者名/発表者名: Hiroshi Chuman, Toshio Fujita, Seiji Hitaoka, Eri Kori, Tatsusada Yoshida
  • 学会等名: CMTPI 2009 (Fifth International Symposium on Computational Methods in Toxicology and Pharmacology Integrating Internet Reseour)
  • 発表場所: Istanbul, Turkey
  • 年月日: 2009-07-05
• [学会発表] Comparative QSAR Analysis of a Series of Benzene Sulfonamide Inhibitors Using Ab Initio Fragment MO Calculation of Their Complex Structures with Carbonic Anhydrase (2009)
  • 著者名/発表者名: Tatsusada Yoshida, Yohei Munei, Koji Hirozumi, Hiroshi Chuman
  • 学会等名: CMTPI 2009 (Fifth International Symposium on Computational Methods in Toxicology and Pharmacology Integrating Internet Reseour)
  • 発表場所: Istanbul, Turkey
  • 年月日: 2009-07-05
• [学会発表] Positive Feedback of Caspase Activation as a Possible Mechanism of Life-Death Decision in Fas Signaling-Induced Apoptosis (2008)
  • 著者名/発表者名: Noriaki Okazaki, Hiroshi Chuman
  • 学会等名: The 2008 Annual Conference of the Japanese Society for Bioinformatics (JSBi2008)
  • 発表場所: Osaka
  • 年月日: 2008-12-15
• [学会発表] Links between QSAR and Molecular Simulation (2008)
  • 著者名/発表者名: Hiroshi Chuman
  • 学会等名: The Annual Meeting 2008 of Korean Society for Bioinformatics and Systems Biology, Cheong-joo
  • 発表場所: Korea
  • 年月日: 2008-11-13
• [学会発表] Theoretical Consideration on Enzymatic QSAR ; Energy Decomposition Analysis of the Hammett Constant and QSAR of MMP-9 Inhibitors Using Ab Initio MO Calculations (2008)
  • 著者名/発表者名: Kazuya Nagaoka, Miku Oonishi, Tatsusada Yoshida, Hiroshi Chuman
  • 学会等名: The 8th China-Japan Joint Symposium on Drug Design and Development
  • 発表場所: Kobe
  • 年月日: 2008-11-06
• [学会発表] Reprofiling the HanschFujita Type of Classical QSAR Using Modern Molecular Calculations (2008)
  • 著者名/発表者名: Tatsusada Yoshida, Kazuya Nagaoka, Toshio Fujita, Hiroshi Chuman
  • 学会等名: The 8th China-Japan Joint Symposium on Drug Design and Development
  • 発表場所: Kobe
  • 年月日: 2008-11-03
• [学会発表] QSAR Study of Cyclic Urea Type HIV-1 Protease Inhibitors Using Ab Initio MO Calculation of Their Complex Structures with HIV-1 Protease (2008)
  • 著者名/発表者名: Hiroshi Chuman, Tatsusada Yoshida
  • 学会等名: French-Japanese Workshop on Computational Methods in Chemistry, Strasbourg
  • 発表場所: ULP
  • 年月日: 2008-06-26
• [図書] QSAR研究の最前(次世代創薬テクノロジー/実践:インシリコ創薬の最前線)NO.14 (2009)
  • 著者名/発表者名: 中馬寛、吉田達貞
  • 総ページ数: 112-116
  • 出版者: 株式会社メディカルドゥ
• [図書] 薬学領域の機器分析学 (2008)
  • 著者名/発表者名: 中馬寛, 他
  • 総ページ数: 77-99
  • 出版者: 株式会社廣川書店