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研究生:陳南佑
研究生(外文):Nan-yow Chen
論文名稱:折疊具有螺旋及平板結構蛋白質的簡化模型
論文名稱(外文):Folding Proteins with Both Alpha and Beta Structures in a Reduced Model
指導教授:牟中瑜蘇正耀蘇正耀引用關係
指導教授(外文):Chung-Yu MouZheng-Yao Su
學位類別:博士
校院名稱:國立清華大學
系所名稱:物理學系
學門:自然科學學門
學類:物理學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:英文
論文頁數:107
中文關鍵詞:蛋白質折疊簡化模型二級結構螺旋結構及平板結構等效位能粗粒化的表現蛋白質折疊問題氫鍵偶極-偶極交互作用局域親疏水性交互作用
外文關鍵詞:protein foldingreduced modelsecondary structureshelix and sheet structureseffective potentialcoarse-grained representationprotein folding problemhydrogen bondsdipole-dipole interactionslocal hydrophobic interactions
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我們提出一個可以同時折疊出螺旋及平板結構的簡化模型來研究所謂的蛋白質折疊問題。此模型的主要目的是找到一個包含水的效應而且沒有人為外加作用的等效位能,同時,可以在合理的時間內預測出給定序列蛋白質的三維結構。為了達到這個目的,此模型並不考慮整個折疊的動力過程或是原子尺度下的完整結構之描述,而是採用蒙地卡羅方法以及粗粒化的蛋白質結構表現。這粗粒化的蛋白質結構表現是用符合已知結構的特定幾何物件來表示蛋白質的側鏈和骨幹上的胜肽平面。藉此粗粒化的表現,此模型的等效位能可以被設計出來。此外,在這模型中引進了兩個新的交互作用:偶極-偶極交互作用以及局域親疏水性交互作用。這兩個新的交互作用與氫鍵同為形成蛋白質二級結構之關鍵要素。由於這兩種交互作用的加入,此模型可以在不用任何人為外加作用下,同時折疊出螺旋及平板兩種二級結構。進一步的分析指出,此模型亦可以在合理的精確度下折疊出其它的蛋白質。因此,對於解決蛋白質折疊問題,此模型提供了一個可能的起點。
A reduced model, which can fold both helix and sheet structures, is proposed to study the problem of protein folding. The goal of this model is to find an unbiased effective potential that has included the effects of water and at the same time can predict the three dimensional structure of a protein with a given sequence in reasonable time. For this purpose, rather than focusing on the real folding dynamics or full structural details at the atomic scale, we adopt the Monte Carlo method and the coarse-grained representation of the protein in which both side-chains and the backbones are replaced by suitable geometrical objects in consistent with the known structure. On top of the coarse-grained representation, our effective potential can be developed. Two new interactions, the dipole-dipole interactions and the local hydrophobic interactions, are introduced and are shown to be as crucial as the hydrogen bonds for forming the secondary structures. In particular, for the first time, we demonstrate that the resulting reduced model can successfully fold proteins with both helix and sheet structures without using any biased potential. Further analyses show that this model can also fold other proteins in reasonable accuracy and thus provides a promising starting point for the problem of protein folding.
Abstract
List of Figures
List of Tables
1 Introduction
2 Essentials of Proteins Structures and Numerical Methods
2.1 Building Blocks and Level of Protein Structures
2.2 Monte Carlo Method
3 Reduced Protein Folding Model (RPFM)
3.1 Coarse-Grained Representation of the Protein
Molecules
3.1.1 Backbone Units
3.1.2 Side-chain Units
3.2 Interaction Potentials
3.3 Relative Energy Strengths and Conformation Parameters
3.3.1 Relative Energy Strengths
3.3.2 The Ramachandran Potential Plots
3.3.3 Conformation Parameters
4 Simulation Results and Analysis
4.1 Simulation Results
4.1.1 One Alpha Helix Case
4.1.2 One Beta Sheet Case
4.1.3 One Alpha Helix and One Beta Sheet Case
4.1.4 Heat Capacity
4.1.5 Effects of Dipole-Dipole Interactions and Local
Hydrophobic Interactions
4.2 Real Protein Peptides
5 Conclusions and Outlook
Appendix A
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