2018 Fiscal Year Final Research Report
Molecular mechanism of amino-acid selection in protein synthesis
| Project/Area Number |
16K18532
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biophysics
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| Research Institution | Kitasato University (2017-2018)
Institute for Molecular Science (2016) |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | スレオニルtRNA合成酵素 / 分子動力学シミュレーション / 配列解析 / 共変異解析 / 結合親和性 / 結合自由エネルギー / リガンド選択性 |
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| Outline of Final Research Achievements |
Aminoacyl-tRNA synthetase (AARS) catalyzes the aminoacylation of tRNA. The aminoacylation of tRNA is needed before protein synthesis in ribosomes. Therefore the function of AARS is important.
In this study, we used a threonyl-tRNA sythetase (ThrRS) to study threonine binding to ThrRS and its molecular insights. This enzyme selects a threonine molecule and the threonine molecule binds to ThrRS. Similar amino acids such as valine and serine are not bonded to a tRNA corresponding to threonine. We studied the selection mechanism of a threonine molecule in ThrRS using molecular dynamics simulations, quantum chemical calculations, and a multiple sequence alignment. We found that several amino acid residues are highly conserved and that these amino acid residues contribute the free energy profile of the ligand binding in threonyl-tRNA synthetase.
We revealed the molecular mechanism of the selection of a threonine molecule in ThrRS using several theoretical and bioinformatics methods.
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| Free Research Field |
生物物理学
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| Academic Significance and Societal Importance of the Research Achievements |
本課題の研究成果を出すにあたって，計算生物学における様々な手法を用いた。例えば分子科学分野における分子動力学シミュレーションや量子化学計算，バイオインフォマティクスにおける配列解析を行った。これらの手法の融合により，物理化学的および生物学的な理解を同時に得ることができるようになった。
また本課題の対象となったタンパク質は細菌に対する抗生物質の対象となっており，アミノ酸の結合機構を理解することは，このような薬物の作用機序に対する新しい理解をもたらすことになると期待される。
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