A theoretical verification of the ligand-binding-pathway hypothesis
Project/Area Number |
15K07021
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Biophysics
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Research Institution | The University of Tokyo |
Principal Investigator |
Terada Tohru 東京大学, 大学院農学生命科学研究科(農学部), 特任准教授 (40359641)
|
Research Collaborator |
NEGAMI Tatsuki 東京大学, 大学院農学生命科学研究科, 特任研究員
|
Project Period (FY) |
2015-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
Keywords | 分子動力学シミュレーション / タンパク質 / リガンド / パスウェイ / 粗視化モデル / 自由エネルギープロファイル / マルコフ状態モデル / transition path theory / リガンド結合パスウェイ / 最小自由エネルギー経路 / タンパク質-リガンド結合 / リガンド結合シミュレーション / 粗視化分子動力学法 / 変異体 |
Outline of Final Research Achievements |
I performed many runs of a coarse-grained molecular dynamics simulation for a protein-ligand system, where the ligand molecules were randomly placed around the protein. I constructed a Markov state model from the trajectories. Furthermore, I analyzed the model based on the transition path theory to find the transition state and ligand-binding pathways. As a result, it was shown that the transition state is located around the rim of the substrate-binding pocket and the ligand-binding pathways that have large contributions to the ligand binding tend to go along the grooves on the protein surface. This result supports the ligand-binding-pathway hypothesis we have proposed.
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Report
(4 results)
Research Products
(8 results)