利用多重粒子碰撞法模擬生物分子之行為

Abstract

我們使用多重粒子碰撞法（multi-particle collision dynamics，MPCD模擬法）配合分子模擬法(molecular dynamics) 模擬生物分子之行為，包括DNA在不同侷限通道所呈現之靜態動態性質，以及觀察脂雙層之平衡和自組裝現象，並將結果與近年相關的實驗或模擬結果相驗證。 MPCD模擬法屬於介觀尺度的模擬，可經由粗化（coarse-grained）過程大幅降低系統所需計算的流體粒子數以提升效率，同時還能精確地模擬單純流體的行為。模擬使用之DNA與Lipid皆以bead-spring model描述，但bead數目及相關作用力參數則有所差異，整體系統則以MPCD-MD hybrid method模擬生物分子在流體的行為。 首先，我們以MPCD法中的SRD模擬法模擬模擬DNA在侷限於平板型狹縫中的行為，模擬所得之靜態與動態性質和DNA鏈長與侷限強度間之關係大致上與近期發表的實驗結果十分接近，同時我們也發現邊界條件之設定會影響DNA之動態性質。使用修正之邊界條件並與blob theory比較後，發現DNA之性質較接近Zimm blob。 其次，我們以相同方法模擬DNA在橫跨奈米通道及微米通道介面時回縮捲曲現象。首先，我們設定一以奈米通道連接左右微米區域之系統，將平衡之DNA置入此系統後，可觀察到DNA橫跨兩個微奈米界面間之拉鋸行為。當此暫態平衡被破壞之後，DNA之一端將會被拉進奈米通道內並且從另一端之微米區域脫離。近期實驗觀察到此DNA 回縮過程可以兩種不同之鬆弛模式描述，我們在模擬中也觀察到了一樣的現象。 最後我們利用bead-spring model建構了脂質模型，並且測試脂雙層於不同溫度下之平衡型態，比較order parameter及two dimensional radial distribution function後其受溫度影響之表現與我們預期相同。接著透過開關作用力使平衡脂雙層均勻分散於系統，進而模擬出脂雙層之自組裝行為。 經由這一系列的研究，我們已建立了一套在介觀尺度下模擬多種生物分子的可靠方法，未來將以此研究為基礎，進一步模擬包含DNA和lipids的複雜系統。

We simulate the behavior of biomolecules by using multi-particle collision dynamics and molecular dynamics hybrid method. We examine the static and dynamic properties of DNA in confinement, the equilibrium and self assembly of lipid bilayer, and make comparison with the recent experimental observation and simulation. MPCD, including SRD and MPC-AT method, is a particle-based mesoscale simulation method which coarse-grains small fluid molecules to large fluid parcels, but it still can simulate the large length scale and long-time scale behavior of pure solvents precisely. The behavior of DNA and lipid are simulated using bead-spring model with different number of beads and force parameters. The complex fluid system consists of simple fluid and biomolecules is then described by the MPCD-MD hybrid method. Firstly, we simulate the behavior of DNA confined in slit-like geometry by SRD method. The scaling of static and dynamic properties with DNA length and slit height agrees with recently experiment results. We also find that the boundary condition matters. We compare the results with blob theory and find the properties of blobs in confinement are close to Zimm blob. Secondly, we use the same method to simulate simulate DNA recoiling process at a nano-micro interface. The sysesm contains two micro cuboids combined by a nano channel. At first, we put a DNA inside the system to observe the tug-of-war behavior at the nano-micro interface. DNA will entirely enter the nano channel and eacape from one side to the other side once the transient equilibrium has been broken. Our simulation shows that there are two different relaxation modes, which has also been observed experimentally, during the recoiling process. Finally, we simulate the behavior of eqilibrium lipid bilayer under different temperature and test orientation order parameter and two dimensional radial distribution function. The result shows that the behavior is the same as expected. By turning on/off some potential, we can uniformly distribute the lipid and then simulate the self assembly of lipid bilayer. In our research, we establish a solid method to simulate different kinds of biomolecules under mesoscale. In the future, we will further simulate complex system containing DNA and lipid.