| Project/Area Number |
12144206
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Osaka University |
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Principal Investigator |
NAKAMURA Haruki Osaka University, Institute for Protein Research, Professor, 蛋白質研究所, 教授 (80134485)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Nobuyuki Kobe University, Clinical Genome Informatics Center, Graduate School of Medicine, Specially Appointed Instructor, 大学院医学系研究科クリニカル・ゲノム・インフォマティクスセンター, 特命講師 (60324852)
中川 敦史 大阪大学, たんぱく質研究所, 助教授 (20188890)
木寺 詔紀 京都大学, 大学院・理学研究科, 助教授 (00186280)
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| Project Period (FY) |
2000 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥27,600,000 (Direct Cost: ¥27,600,000)
Fiscal Year 2004: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2003: ¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 2002: ¥8,500,000 (Direct Cost: ¥8,500,000)
Fiscal Year 2001: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Keywords | Molecular Dynamics / Homology Modeling / Molecular Recognition / Simulation / Supramolecular Structure / Molecular Surface / Brownian Dynamics / Database / チャネル蛋白質 / ループ構造 / 構造探索 / マルチカノニカル統計 |
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| Research Abstract |
Methods were developed for building tertiary structural models of channel proteins, by combining the inductive homology modeling method and the deductive molecular simulation for low-homologous regions. In particular, we developed a new model building method for flexible loop regions, based on the Force-Biased Multicanonical Molecular Dynamics (FB-McMD) with the implicit solvent model using the generalized Born approximation. This method could give us a precise protein model structure even for the flexible loop regions, and it was applied to modeling of actual channel proteins. In addition, protein functions with their sites and protein-protein interaction pairs were identified and predicted with the informatics technology using our new databases, eF-site and HINTdb, respectively.
In order to analyze the molecular recognition of channel proteins, we have developed a new NMR analysis method, where the complexed structure is produced by molecular dynamics simulations using the cross saturation transfer and the residual dipolar coupling signals. This method was applied to build a complexed model between KcsA K^+-channel and agitoxin-2. Brownian dynamics simulation method was also developed for computing permeation of small ions and compounds through a channel protein.
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