kinetic constants of molecular binding calculated from equilibrium
| Project/Area Number |
16K05517
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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 |
Biological physics/Chemical physics/Soft matter physics
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| Research Institution | University of Hyogo (2018-2019)
Osaka University (2016-2017) |
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Principal Investigator |
Higo Junichi 兵庫県立大学, シミュレーション学研究科, 特任教授 (80265719)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 分子動力学シミュレーション / 自由エネルギー計算 / 状態遷移 / 反応座標 / 多次元 / AI / GA / 生体高分子 / 構造変化 / 速度定数 / 遷移確率 / 自由エネルギー地形 / 仮装系 / 自由エネルギー / 効率的サンプリング / カノニカルサンプリング / 平衡定数 / アダプティブアンブレラ / 構造サンプリング / generalized ensemble / enhanced sampling / 生物物理一般 / 分子動力学 / 平衡論 / 速度論 |
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| Outline of Final Research Achievements |
We tried to calculate kinetic constants for molecular binding/unbinding from an generalized ensemble (GE) simulation, which is an equilibrium simulation. A mathematical formulation for the kinetic-constant calculation was obtained. In the GE simulation, bias forces are always applied to atoms constructing the system. We noticed that my formulation is useful to obtain kinetic constants for molecular motions occurring in a very short time period because of the bias forces.
To increase the time scale of the molecular motions, we generated a new GE method, which is free from the bias force. We named this method 'mD-VcMD' simulation (a paper was publihsed). To increase the sampling efficiency further, we integrated mD-VcMD and a AI technique, genetic algorithm, and named the integrated method 'GA-based mD-VcMD' simulation. Three papers are now submitted to journals.
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| Academic Significance and Societal Importance of the Research Achievements |
当研究課題によって、新たな効率的構造探索法である GA-based multi-dimensional virtual-system coupled molecular dynamics (GA-based mD-VcMD) simulation 法を開発した。この手法は、すでに分子動力学 (MD) プログラム（gromacs や omegegine/myPrestyo）に実装して動くようになっている。この手法を用いて、薬物候補化合物と受容体蛋白質との複合体構造予測の研究を行い、実験で得られた複合体構造との一致を確認した。今後、創薬をはじめとした研究に利用されることが期待できる。
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Report
(5 results)
Research Products
(20 results)
