2022 Fiscal Year Final Research Report
Novel molecular design of flourophores by QM/MM molecular dynamics simulations
| Project/Area Number |
20H02701
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 32010:Fundamental physical chemistry-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Yagi Kiyoshi 国立研究開発法人理化学研究所, 開拓研究本部, 専任研究員 (30401128)
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| Co-Investigator(Kenkyū-buntansha) |
花岡 健二郎 慶應義塾大学, 薬学部(芝共立), 教授 (70451854)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | QM/MM計算 / 蛍光イメージング / タンパク質・リガンド相互作用 / 蛍光プローブ |
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| Outline of Final Research Achievements |
The QM/MM method is a multi-scale method, which combines quantum chemical (QM) calculations with molecular mechanics force fields (MM). In this project, the QM/MM method was used to calculate the structure and dynamics of fluorescent probes in a protein environment. The binding of a protein and a fluorescent probe, and the conformational changes induced by electronic excitation were calculated by the QM/MM molecular dynamics simulations to elucidate the molecular mechanism of fluorescence emission. Furthermore, based on the obtained knowledge, we were able to successfully design a novel fluorescent probe that specifically emits fluorescence upon binding to a target protein. A paper presenting the results of this research was published in JACS (JACS 2022, 144, 19778-19790). There has also been a great deal of technical progresses in both computation and synthesis, with 15 related papers published and 26 conference presentations (20 invited talks).
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| Free Research Field |
理論計算化学
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| Academic Significance and Societal Importance of the Research Achievements |
蛍光イメージングは、標的タンパク質を蛍光ラベル化することで、その細胞内動態の直接観察を可能にする、生命科学研究に必要不可欠な手法である。最近、タグタンパク質-蛍光プローブが新たなラベル化手法として注目を集めているが、その光機能制御にはまだ課題があった。本研究では、理論計算と有機合成で共同し、蛍光プローブとタンパク質の相互作用と光化学過程を原子レベルで解明し、「結合すると光る」新しい性質を持った蛍光プローブの設計に成功した。本研究で得られた技術は生体環境中の光機能分子へ広く適用できる。今後、特定のタンパク質の蛍光標識や光免疫療法に有効なプローブ分子の分子設計など、幅広い応用の可能性がある。
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