Signal Transduction Process of G-Protein Coupled Receptor (GPCR) Studied by Molecular Dynamics Simulation
| Project/Area Number |
16H06164
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biophysics
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| Research Institution | University of Tsukuba |
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Principal Investigator |
HARADA Ryuhei 筑波大学, 計算科学研究センター, 准教授 (60612174)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥20,540,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥4,740,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
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| Keywords | Gタンパク質共役受容体 / 分子動力学シミュレーション / タンパク質の構造探索 / 生物物理学 |
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| Outline of Final Research Achievements |
G Protein Couple Receptor (GPCR) is an important membrane protein that transfers several signals from the outer to inner membrane upon the ligand binding. However, its mechanism of signal transduction process has not revealed yet. In the present study, We have developed a set of computational methods (path sampling methods) to address the signal transduction process of GPCR. In more detail, a set of two enhanced sampling methods called "Parallel Cascade Selection Molecular Dynamics (PaCS-MD)" and "Outlier Flooding Method (OFLOOD)" has been combined as a hybrid path search method and it was applied to the GPCR system. In the current status, we are now analyzing trajectories (transition path trajectories related to the signal transduction of GPCR) generated by the hybrid conformational sampling method.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究において, GPCRなどの巨大システムの反応経路探索に適用可能な計算手法を開発したことで, GPCR以外の重要な生体分子にも適用可能な堅牢な方法論を提供することができた. 開発手法は, 様々な研究者に利用可能な様に一般公開を進めており, 今後社会還元していく予定である. また, GPCRは創薬設計においてレセプターとしても注目されている重要なタンパク質であり, 細胞内外におけるシグナル伝達経路のメカニズムの解明が進むことは, 合理的な新薬設計に与える影響も大きいと考えられ, 更なる社会還元が期待される.
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Report
(4 results)
Research Products
(47 results)
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[Journal Article] Classical cumulant dynamics for statistical chemical physics2017
Author(s)
Yasuteru Shigeta, Ryuhei Harada, Ryuma Sato, Hirotaka Kitoh-Nishioka, My Bui Thi Kieu, Akimasa Sato, Takaki Tokiwa, Akane Kyan, Yuki Ishii, Masato Kimatsuka, Sotaro Yamasaki, Megumi Kayanuma, Mitsuo Shoji
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Journal Title
Molecular Simulation
Volume: 43
Issue: 13-16
Pages: 1260-1268
DOI
Related Report
Peer Reviewed
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[Journal Article] Molecular mechanisms of substrate specificities of uridine-cytidine kinase2016
Author(s)
W. Tanaka, M. Shoji, F. Tomoike, Y. Ujiie, K. Hanaoka, R. Harada, M. Kayanuma, K. Kamiya, T. Ishida, R. Masui, S. Kuramitsu, Y. Shigeta
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Journal Title
Biophysics and Physicobiology
Volume: 13
Issue: 0
Pages: 77-84
DOI
NAID
ISSN
2189-4779
Related Report
Peer Reviewed
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