Influences of Arsenic/Phosphorus Swap on the Structural, Dynamical, and Electronic Properties of Lipid Bilayers and Double Stranded DNA: A Multi-Scale Computational Study

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姓名

黃建銘(Jian-ming Huang) 查詢紙本館藏

畢業系所

化學學系

論文名稱

(Influences of Arsenic/Phosphorus Swap on the Structural, Dynamical, and Electronic Properties of Lipid Bilayers and Double Stranded DNA: A Multi-Scale Computational Study)

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摘要(中)

生物分子主要由六個的化學元素所組成：碳、氫、氮、氧、磷、硫。最近的研究發現在GFAJ-1細菌中，砷元素可能取代生物分子上的磷元素並維持其生命。此外，也有文獻指出含砷的有機小分子其水解半衰期時間太短而被認為無法存在於有水的環境。雖然這個議題仍存在爭議。在本篇研究中，我們利用分子動態模擬和泛函密度函數理論來研究含砷的生物分子和一般的生物分子之間在性質上的差異。
第一個部分，我們使用全原子分子動態模擬探討含砷生物膜和一般生物膜在基本膜結構和動態性質上的差異。我們的模擬顯示含砷的生物膜具有獨特的結構和動態性質。含砷的生物膜相對於一般生物膜結構較緊密、膜面積較小和排列比較整齊。含砷生物膜的結構緊密是由於脂質之間形成較強鹽橋所引起，鹽橋將含砷的脂質吸引在一起，降低脂質頭基的旋轉速度和脂質的擴散。因此，含砷生物膜和一般生物膜之間有不同的動態性質，因此也可能會出現不同的生物功能。
第二個部分，我們使用density functional theory探討由5個鹼基對組成的DNA，在砷和磷之間的轉換會如何影響構形和電子性質。研究結果顯示，M06-2X方法可得到較接近實驗結果的DNA結構，而常用的B3LYP方法則產生較大的和實驗結果的偏差。計算得到的DNA是屬於BI的構形，和實驗結果相同，而當磷轉換成砷計算得到的結構仍然是一個BI構形。含砷DNA和一般DNA雖然都擁有BI的構形，不過，結構之間仍有差異，例如:親疏水性質，DNA溝槽大小，DNA螺旋性質。有趣的是，含砷DNA具有較強的紫外線吸收強度，因此含砷DNA可能比較容易在紫外線照射下產生結構的損壞。

摘要(英)

Biomolecules are composed mainly of six major chemical elements: carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur. Recent studies have suggested the possibility of sustaining life if the phosphorus is substituted by arsenic. Although this issue is still controversial, it is interest to investigate the properties of arsenated-lipid bilayers and arsenated-DNA to evaluate the possibility.
In the first part, we simulated arsenated-lipid, 1-palmitoyl-2-oleoyl-sn-glycero-3- arsenocholine (POAC), lipid bilayers using all-atom molecular dynamics to understand basic structural and dynamical properties, in particular, the differences from analogous 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, (POPC) lipid bilayers. Our simulations showed that POAC lipid bilayers have distinct structural and dynamical properties from those of native POPC lipid bilayers. Relative to POPC lipid bilayers, POAC lipid bilayers have a more compact structure with smaller lateral areas and greater order. The compact structure of POAC lipid bilayers is due to the fact that more inter-lipid salt bridges are formed with arsenate-choline compared to the phosphate-choline of POPC lipid bilayers. These inter-lipid salt bridges bind POAC lipids together and also slow down the head group rotation and lateral diffusion of POAC lipids. Thus, it would be anticipated that POAC and POPC lipid bilayers would have different biological implications.
In the second part, we study the double-stranded native and As-substituted DNA with five base pairs using density functional theory to investigate the impacts on the conformational and electronic properties upon arsenic/phosphorus interchange. The Minnesota density functional M06-2X well reproduces of the experimental structure of native DNA; while the commonly used B3LYP functional yields large deviation. The optimized structure of native DNA at M06-2X/6-31G(d,p) level is BI-form conformation, which is consistent with the experimental result. Interestingly, the optimized structure of As-DNA at M06-2X/6-31G(d,p) level also remains a BI-form conformation. The structures of native and arsenated-DNA share some common structural features; nevertheless, they have some differences such as hydrophobic core, DNA groove, and helix twist. More interestingly, the As-DNA has stronger molar absorbance than native DNA suggested that As-DNA might be damaged quickly than native DNA under UV radiation.

關鍵字(中)

★ 砷元素

關鍵字(英)

★ arsenic-loving life
★ arsenated-lipid
★ arsenated-DNA
★ arsenate-choline salt bridge

論文目次

摘要 i
Abstract ii
致謝 iv
Table of Contents v
List of Figures vi
List of Tables viii
一、Introduction 1
二、Section I - Arsenated-lipid Bilayers 4
1. Computational Methods 5
1.1. Arsenate Force Field Parameterization 5
1.2. Molecular Dynamics Simulations 7
2. Results and Discussion 9
2.1. Area per Lipid and Membrane Thickness 9
2.2. Atom Distribution 10
2.3. Order Parameters 11
2.4. Dynamics of Lipids 12
3. Conclusions and Summary 15
三、Section II - Arsenated-DNA 16
1. Computational Methods 17
2. Results and Discussion 18
2.1. Framework of DNA Structure 18
2.2. Helical Parameters 20
2.3. Glycosyl and Backbone Conformation 22
2.4. Geometries 23
2.5. Binding Energy 23
2.6. UV-Vis Spectra 24
3. Summary and Conclusion 25
References 26

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指導教授

蔡惠旭(Hui-hsu Tsai)

審核日期

2013-7-23

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