| Project/Area Number |
17F17819
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Single-year Grants |
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| Section | 外国 |
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| Research Field |
Biophysics
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| Research Institution | Nagoya University |
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Principal Investigator |
TAMA FLORENCE 名古屋大学, 理学研究科, 教授 (20648191)
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| Co-Investigator(Kenkyū-buntansha) |
RAKERS CHRISTIN 名古屋大学, 理学(系)研究科(研究院), 外国人特別研究員
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| Project Period (FY) |
2017-11-10 – 2018-03-31
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| Project Status |
Discontinued (Fiscal Year 2017)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2017: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | striga / MD simulations |
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| Outline of Annual Research Achievements |
Based on X-ray crystal structure of Striga receptor ShHTL5, homology models of ShHTL7 were developed and validated. In addition, models of a collection of experimentally investigated HTL7 mutants (amino acid residue changes in the receptor’s active site) were created. These structures were submitted to MD simulations to explore their structural flexibility. The analyses of resulting MD trajectories showed significantly higher plasticity of HTL7 protein helices that surround the active site of HTLs compared to HTL5. The degree of flexibility decreases with increasing number of single residue changes from HTL7 towards HTL5. The increased flexibility in HTL7 is found to be in accordance with experimental assay results that indicate that HTL7 is more promiscuous with regard to ligand binding compared to other HTLs.
The developed homology models of HTL7 and the published structure of HTL5 were further used as basis for induced fit docking studies with experimentally validated active molecules. The purpose of these docking studies was to (i) computationally assess the structure-activity relationship of tested small molecules and Striga receptors and to identify essential protein-ligand interactions that lead to receptor modulation, and (ii) to create an ensemble of structural complexes with highly potent molecules for subsequent protein-ligand MD simulations. These could be used for the development of 3D dynophore models that would allow virtual screening of chemical libraries.
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| Research Progress Status |
29年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
29年度が最終年度であるため、記入しない。
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