kinetic constants of molecular binding calculated from equilibrium

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K05517
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological physics/Chemical physics/Soft matter physics
• Research Institution: University of Hyogo (2018-2019); Osaka University (2016-2017)
• 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)
• Project Period (FY): 2016-04-01 – 2020-03-31
• 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

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.

Free Research Field

生物物理学

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。