Molecular Recognition of Binding Site for the Geometrical Flexibility of Bioactive Ligands

• Project/Area Number: 15590043
• 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: GOTO Satoru University of Tokushima, Institute of Health Bioscience (HBS), Research Associate, 大学院・ヘルスバイオサイエンス研究部, 助手 (50253232)
• Co-Investigator(Kenkyū-buntansha): MUNAKATA Tatsuo Tohwa University, Faculty of Engineerings, Lecturer, 工学部, 講師 (30320261) ; TERADA Hiroshi Tokyo University of Science, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (00035544)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: Puckering Coordinates / Manifold / Principle Component Analysis / cyclic compound / cycloalkane / erythromycin / ciguatoxins / conformation analysis / クラスター分析 / リガンド-タンパク質相互作用

Research Abstract

The structure changes through the process of the ligand bindings to the binding site of the receptor proteins and the structure of ligand induced a three-dimensional complementarity mutually. The computation of the significant frequency in the statistical thermodynamics when this is analyzed by using the simulation technique of the molecular dynamics method etc. is required.
However, though the equivalent large memory capacity is needed when the network structure data approved by calculating the snap shot of the space covering it when the moment of the space momentarily is caught at 4th Dimension of the combination of an affiliated change at that time with the protein structure, and analyzing those interrelations is analyzed, the calculation load decreases rapidly compared with the repetition of the simulation because the calculation frequency of each route like becoming statistically effective it is finished by the calculation frequency once. A dynamic space in the protein structure of the protein molecule and the ligand is calculated in the generation of the snap shot of the space covering it at the particular 4th Dimension, and the technique for verifying the spatial combination can be applied.
Then, Conformation of the molecule was generated covering it by calculating Monte Carlo to clarify what one dynamic spaced about a molecular structure, the internal coordinates were constructed, and the system that generated an independent solution space was constructed with the principal ingredient analysis at time. When this calculation result was examined in detail, it was clarified to the compound with the ring structure that the solution space corresponding to the characteristic of the ring structure appeared. Then, a mathematical principle that estimated the topology of the solution space of the material that had a more complex protein structure was clarified by catching the relation between the structure and the solution space as the phase geometrical in three dimension figure.

Research Products

• [Journal Article] 1-Alkyl(aryl)(tetrafluoroborate)-λ^3-bromanes as highly efficient Michaek acceptors : Uncatalyzed conjugate addition of 1-alkynyl(trialkyl)stannanes yielding symmetrical and unsymmetrical 1,3-butadiynes (2005)
  • Author(s): Ochiai, M.
  • Journal Title: Angewandte Chemie International Edition 44 Pages: 406-409
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Alkyl(aryl)(tetrafluoroborate)-λ^3-bromanes as highly efficient Michael acceptors : Uncatalyzed conjugate addition of 1-alkynyl(trialkyl)stannanes yielding symmetrical and unsymmetrical 1,3-butadiynes (2005)
  • Author(s): Ochiai, M., Nishi, Y., Goto, S., Frohn, H.J.
  • Journal Title: Angew.Chem.Int.Ed. 44 Pages: 406-409
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 1-Alkyl(aryl)(tetrafluoroborate)-λ^3-bromanes as highly efficient Michaek acceptors : Uncatalyzed conjugate addition of 1-alkynyl... (2005)
  • Author(s): Ochiai, M.
  • Journal Title: Angewandte Chemie International Edition 44 Pages: 406-409
• [Journal Article] Intramolecular nonbonded S-O interaction in actazolamide and thiadiazolinethione molecules in their dimeric crystalline structures and complex crystalline structures with enzymes (2004)
  • Author(s): Nagao, Y.
  • Journal Title: Tetahedron Letters 45 Pages: 8757-8761
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] New ring expansion reactions of hydroxyl propenoyl cyclic compounds under palladium(0)/phosphine-catalyzed conditions (2004)
  • Author(s): Nagao, Y.
  • Journal Title: Organic Letters 24 Pages: 2133-2136
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Mechanistic consideration for the consecutive cyclization of 2,3-dibromopropylamines hydrobromide giving a strained molecule, 1-azabicyclo[1.1.0]butane (2004)
  • Author(s): Hayashi, K.
  • Journal Title: Chemical & Pharmaceutical Bulletin 52 Pages: 89-94
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Intramolecular nonbonded S-O interaction in acetazolamide and thiadiazolinethione molecules in their dimeric crystalline structures and complex crystalline structures with enzymes (2004)
  • Author(s): Nagao, Y., Iimori, H., Honjo, T., Goto, S., Ooi, T., Sano, S., Shiro, M.
  • Journal Title: Tetrahedron Letters 45 Pages: 8757-8761
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] New ring-expansion reactions of hydroxy propenoyl cyclic compounds under palladium(0)/phosphine-catalyzed conditions (2004)
  • Author(s): Nagao, Y., Tanaka, S., Ueki, A., Kumazawa, M., Goto, S., Ooi, T., Sano, S., Shiro, M.
  • Journal Title: Org.Lett. 24 Pages: 2133-2136
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mechanistic considerations for the consecutive cyclization of 2,3-dibromopropylarmine hydrobromide giving a strained molecule, 1-azabicyclo[1.1.0]butane (2004)
  • Author(s): Hayashi, K., Ikee, Y., Goto, S., Shiro, M., Nagao, Y.
  • Journal Title: Chem.Pharm.Bull. 52 Pages: 89-94
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Intramolecular nonbonded S-O interaction in actazolamide and thiadiazolinethione molecules in their dimeric crystalline structure... (2004)
  • Author(s): Nagao, Y.
  • Journal Title: Tetahedron Letters 45 Pages: 8757-8761
• [Journal Article] Mechanistic consideration for the consecutive cyclization of 2,3-dibromopropylamines hydrobromide giving a strained molecule,... (2004)
  • Author(s): Hayashi, K.
  • Journal Title: Chemical & Pharmaceutical Bulletin 52 Pages: 89-94
• [Journal Article] Synthesis, structure, and reaction of l-alkynyl(aryl)-λ^3-bromanes (2003)
  • Author(s): Ochiai, M.
  • Journal Title: Journal of American Chemical Society 125 Pages: 15304-15305
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Mechanistic investigations on the reaction between amines or amides and an alkylperoxy-λ^3-iodane (2003)
  • Author(s): Sueda, T.
  • Journal Title: Journal of Organic Chemistry 18 Pages: 3307-3310
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] α-Tocopheryl succinate activates protein kinase C in cellular and cell-free systems (2003)
  • Author(s): Kogure, K., Hama, S., Goto, S., Munakata, T., Tokumura, A., Fukuzawa, K.
  • Journal Title: J.Nutr.Sci.Vitaminol. 49 Pages: 310-314
  • NAID: 10012074064
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Synthesis, structure, and reaction of 1-alkynyl(aryl)-λ^3-bromanes (2003)
  • Author(s): Ochiai, M., Nishi, Y., Goto, S., Shiro, M., Frohn, H.J.
  • Journal Title: J.Am.Chem.Soc. 125 Pages: 15304-15305
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Two lignan dimmers from bamboo stems (Phyllostachys edulis). (2003)
  • Author(s): Suga, A., Takaishi, Y., Goto, S., Munakata, T., Yamauchi, I., Kogure, K.
  • Journal Title: Phytochemistry 64 Pages: 991-996
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mechanistic investigations on the reaction between amines or amides and an alkylperoxy-λ^3-iodane (2003)
  • Author(s): Sueda, T., Kajishima, D., Goto, S.
  • Journal Title: J.Org.Chem. 18 Pages: 3307-3310
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Secondary hypervalent I (III)【triple bond】O interactions : Synthesis and structure of hypervalent complexes of diphenyl-λ^3-iodanes with 18-crown-6 (2003)
  • Author(s): Ochiai, M., Suefuji, T., Miyamoto, K., Tada, N., Goto, S., Shiro, M., Sakamoto, S., Yamaguchi, K.
  • Journal Title: J.Am.Chem.Soc. 125 Pages: 769-773
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Synthesis, structure, and reaction of 1-alkynyl(aryl)-λ^3-bromanes (2003)
  • Author(s): Ochiai, M.
  • Journal Title: Journal of American Chemical Society 125 Pages: 15304-15305
• [Publications] K.Hayashi et al.: "Mechanistic consideration for the consecutive cyclization of 2,3-dibromopropylamine hydrobroumide"Chem.Pharm.Bull.. 52(1). 89-94 (2004)
• [Publications] K.Kogure et al.: "α-Tokopheryl succinate activates protein kinase C in cellular and cell-free systems"J.Nutr.Sci.Vitaminol.. 49. 310-314 (2003)
• [Publications] M.Ochiai et al.: "Synthesis, Structure, and Reaction of 1-Alkynyl(aryl)-λ^3-bromanes"J.Am.Chem.Soc.. 125(50). 15304-15305 (2003)
• [Publications] A.Suga et al.: "Two lignan dimers from bamboo stems (Phyllostachys edulis)"Phytochemistry. 64. 991-996 (2003)
• [Publications] T.Sueda et al.: "Mechanistic investigations on the reaction between amines or amides and an alkylperoxy-λ^3-iodane"J.Org : Chem.. 68. 3307-3310 (2003)
• [Publications] M.Ochiai et al.: "Secondary Hypervalent I(III)。トO Interactions : Synthesis and Structure of Hypervalent Complexes of Diphenyl"J.Am.Chem.Soc.. 125(3). 769-773 (2003)