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研究生(外文):Chan Lan Shang
論文名稱(外文):Molecular dynamics simulation and essential dynamic analysis of vigna raddiate plant defensin 1
指導教授(外文):Ping-Chiang Lyu
外文關鍵詞:molecular dynamics simulationvigna radiate plant defensinessential dynamic
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綠豆防禦素第一型(VrD1)為一種植物防禦素。是第一個被報導具有抵抗豆象蟲能力的植物防禦素。在我們之前的研究中,該植物防禦素可能藉由抑制α-澱粉水解酶而達到抗蟲的功效。雖然該植物防禦素的結構已被我們實驗室解出,可是它的抗蟲機制還不是很清楚。根據之前的研究,在其他的防禦素中並未發現像是綠豆防禦素第一型一樣的310 螺旋結構的。該310 螺旋結構很可能與綠豆防禦素第一型的抗蟲能力有關。該防禦素中的第二十六個精胺酸 (Arg26) 與第十個色安酸 (Trp10) 被推測可能與該310 螺旋結構的行成有關。因此,我們藉由分子動力模擬這兩個氨基酸的關係。另外,我們也建立了R26K, R26E 和 W10A 的點突變結構模型並與α-澱粉水解酶嵌合來闡明兩者的結合模式。我們動力模擬的結果顯示第一環型結構 (loop1) 與第三環型結構 (loop3) 在運動上有較高的相關性,這暗示了第一環型結構與第三環型結構之間可能會相互作用。另外,第十個色氨酸也位於第一環型結構上。動力模擬的結果也顯示第二十六個精胺酸與第十個色胺酸之間的相關性也較高的。因此,根據這樣子的結果,當第二十六個精胺酸被置換成離氨基酸 (R26K) 或麩胺酸 (R26E) 時,第十個色氨酸之鏈的方向會被改變進而影響第一環型結構的易曲性,進而影響到第三結構。
Vigna radiata plant defensin 1 (VrD1) is one kind of plant defensins, which is the first report to exhibit the insecticidal activity against bruchid. In our previous studies, this insecticidal activity may be through its inhibitory effect on α-amylase activity. Although VrD1 structure has been determined in our laboratory, the detailed mechanism of this inhibition remains unclear. According to our studies, 310 helix in VrD1 which is not observed in other plant defensins probably plays an important role in this inhibition. Arg26 and Trp10 in VrD1 may be critical for the formation of 310 helix. Therefore, we employed molecular dynamic simulation to investigate the relationship between these two residues. In addition, we also built the models of R26K, R26E and W10A mutants and docked these models to α-amylase to elucidate their binding mode. Our simulation results showed that loop L1 has higher correlation with loop L3, which implied there was interaction between Loop L1 and L3. On the other hand, Trp10 was on loop L1 in VrD1 structure. The simulation results also showed the correlation coefficient between Arg26 and Trp10 was higher. Thus, according our results, when replacing Arg26 to Lys (R26K) or Glu (R26E), the orientation of Trp10 would be changed and this change would effect the flexibility of loop L1, and further influence the fluctuation of loop L3.
謝誌 3

Abstract 4

中文摘要 5

Chapter I. Introduction 6
1.1 Plant defensins 6
1.2 Vigna radiata plant defensin 1 6
1.3 Tenebrio molitor α-Amylase 8
1.3 Molecular dynamic (MD) simulation 9
1.4 The goal of this thesis 10

Chapter II. Theories and algorithms 12
2.1 Force field 12
2.2 Simple point charge water model 12
2.3 Linear constraint solver(LINCS)and SHAKE algorithm 14
2.4 Periodic boundary conditions 14
2.5 Leap-frog integration method 15
2.6 Particle-mesh Ewald(PME) 16
2.7 Temperature and Pressure coupling 16
2.8 NVT and NPT ensemble 17
2.9 Binding free energy 18
2.10 Lennard-Jones(LJ)potential 18
2.11 Root-mean square deviation(RMSD) 19
2.12 Root-mean square fluctuation(RMSF) 19
2.13 Definition secondary structure of protein (DSSP) 20
2.14 Generalized Correlation 20
2.15 Essential Dynamics (ED) 22

Chapter III. Material and method 23
3.1 Operating system & softwares 23
3.2 PDB files of homology model prediction 25
3.3 Process of MD simulation 25
3.4 VrD1 docking with TMA 27

Chapter IV. Results & Discussions 29
4.1 Targets of molecular dynamic simulations 29
4.2 Stability of the simulation systems 29
4.3 Root-mean square fluctuation 30
4.4 Definition secondary structure of protein 31
4.5 Generalized-correlation 31
4.6 Essential Dynamic 33
4.7 Docking with TMA 34

Chapter V. Conclusions 36
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