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Title: | 以同源模擬法預測天蠶素結構 Cecropin A Structure Prediction Using Homology Modelling |
Authors: | Yao-Zong Chen 陳耀宗 |
Advisor: | 王勝仕 |
Keyword: | 同源模擬法,蛋白質結構預測,抗菌胜?,SWISS-MODEL,Modeller,BAM,SWISS-pdbviewer,cecropin a, homology modelling,prediction of protein structure,antimicrobial peptides,SWISS-MODEL,Modeller,BAM,SWISS-pdbviewer,cecropin A, |
Publication Year : | 2014 |
Degree: | 碩士 |
Abstract: | 對於蛋白質的結構有更深入的了解有助於引導誘變實驗設計,而誘變實驗可 以探討與證實結構與功能之間的相關性,在發展新的疾病療法上有相當程度的幫 助。同源模擬法(homology modeling)是一種電腦模擬方法用於蛋白質結構預測,從 具有同源性蛋白質之現存解出結構(可能由 NMR 或 X-ray diffraction 得到)為模板, 模擬出未知序列的蛋白質結構。該方法立基於觀察到蛋白質三級結構和一級結構 相較之下更為保守,因此兩個蛋白質即使在序列下有較大落差,還是有可能存在 相同的折疊方式。同源模擬方法的主要步驟為選擇模板、排比、主鏈與側鏈預測、 結構最佳化及模型評估。模板的選擇最為重要,與能否模擬出正確的結構有很大 關聯;排比是將目標序列與未知序列調整至兩者對應到最佳的同源區域;模型的 主鏈原子將對應到模板的三維結構,因此不保守的側鏈方向也會被預測出來;最 佳化則是透過力場模擬立體空間的障礙,改善原子間的氫鍵作用力關係;最後對 最終模型評估其正確性,找出模型中出現錯誤的區域;而如非保守型的 loop 二級 結構,則需要和保守型區域獨立開來模擬。本研究之實驗分為四個獨立的流程, 包含 SWISS-MODEL 自動化同源模擬、SWISS-pdbviewer、Modeller、BAM 模擬 流程,嘗試得到抗菌胜肽—天蠶素 cecropin a 的三級結構,其中由 BAM 流程分別 基於 1F0H、1D9J、2LA2 等三個模板建構而得之模型,在 GA341 的評分標準下, 符合蛋白質的正確摺疊。本研究提供不同模擬流程的比較,建構出合理的模型。 Better understanding on protein structure can aid in designing mutagenesis experiments, leading to verification of the structure–function relationships and even facilitating the development of new therapeutics for diseases. Homology modelling is an in silico simulation method for protein structure prediction. Modeling structure of query amino acid sequence is based on a homologous template structure experimentally solved by NMR or X-ray diffraction. The construction of homology modelling is based upon the observation that the tertiary structure of proteins is more conserved than their primary structure. This can be used to explain the fact that even two proteins with distinct primary structures may still share the same folding behavior. The key steps in homology modelling are template selection, alignment, backbone and side-chain prediction, structure optimization and model evaluation. The crucial step is template choosing. Inappropriate selection would result in incorrect structures. The purpose of alignment step aims at adjusting the alignment to ensure that the sequences fit optimal correspondence between the homologous regions. In the next step, the backbone atoms of model would be translated to fit the tertiary structure of the template, and the non-conservative side-chains can then be predicted. The optimization step serves to remove the steric clashes and hydrogen-bonding relations between atoms. Finally, the correctness of the model is evaluated and the errors in the model are determined. The non-conservative loops and the conservative regions may be modelled separately. In this thesis, attempt was made to model the tertiary structure of a 37-residue antimicrobial peptide cecropin A using four different methods, including SWISS-MODEL, SWISS-pdb viewer, modeler, and BAM. Through BAM process, we obtained three reliable structures which were built upon the templates of 1F0H, 1D9J, and 2LA2 according to the GA341 scoring critera. In this research, the reliable models were built by comparing different modelling processes. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57053 |
Fulltext Rights: | 有償授權 |
Appears in Collections: | 化學工程學系 |
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ntu-103-1.pdf Restricted Access | 4.74 MB | Adobe PDF |
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