Orbital interaction based binding energy analysis for designing molecular targeted drugs
| Project/Area Number |
16K08321
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | Kyushu University |
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Principal Investigator |
ORIMOTO Yuuichi 九州大学, 総合理工学研究院, 学術研究員 (00398108)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 分子標的薬 / 結合エネルギー / 分子認識 / タンパク質 / 電子状態 / 構造最適化（エネルギー勾配法） / スルースペース／ボンド軌道相互作用 / オーダーN Elongation法 / 蛋白質 |
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| Outline of Final Research Achievements |
In vivo molecular recognition causes with concerted structural changes. The aim here is to develop a new binding energy analysis method for designing the recognition ability in molecular targeted drugs, by which the relationship between the structural changes and binding energy can be obtained from the orbital interaction viewpoint. For the purpose, the through-space/bond (TS/TB) interaction analysis method was combined with geometrical optimization algorism to predict optimized geometries under cutting off the specific interactions and its contribution to the binding energy on recognition reaction. As the first step towards huge bio-systems, the TS/TB method was developed so as to analyze orbital interactions in the unit of region localized molecular orbitals generated by O(N) elongation method. As a related work, the DNA-molecule interaction was investigated and machine learning was adopted to find hidden rules among numerous interaction dataset.
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| Academic Significance and Societal Importance of the Research Achievements |
電子相関効果を含めて実行可能な軌道相互作用解析法と構造最適化を結合した本手法は、分子認識時の構造変化や結合エネルギーへの寄与を相互作用単位で高精度評価できる世界に類のないアプローチである。超高精度O(N) Elongation（ELG）法との完全な結合は現在まだ開発中だが、完成すれば創薬分野に貢献しうる新規結合エネルギー評価法として世界をリードできる。ELG法はあらゆる計算設備（PC～スパコン）に対応可能であり、誰もが身近なPC上で分子標的薬の高精度設計が可能となり、広く難病の原因解明や迅速な薬剤開発に貢献できる。創薬の他、材料・触媒開発等、基礎研究から産業分野まで広く波及効果が期待できる。
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Report
(5 results)
Research Products
(32 results)
