THEORETICAL AND COMPUTATIONAL ANALYSES OF DRUG-RECEPTOR INTERACTION CONSIDERING HYDROPHOBIC INTERACTION

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590036
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: The University of Tokushima
• Principal Investigator: CHUMAN Hiroshi The University of Tokushima, 大学院・ヘルスバイオサイエンス研究部, 教授 (20304545)
• Project Period (FY): 2008 – 2010
• Keywords: 創薬理論計算化学

Research Abstract

We have proposed a novel Quantitative Structure-Activity Relationship (QSAR) involving molecular calculations such as Fragment Molecular Orbital one, and applied this procedure (Linear Expression by Representative Energy terms ; LERE) to several cases of ligands-protein interaction system in order to demonstrate the validity of the LERE procedure. As a result, we confirmed that the procedure provides valuable information which can not be obtained with any other methods.

Research Products

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