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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳倩瑜(Chien-Yu Chen) | |
dc.contributor.author | Hui-Yu Chiang | en |
dc.contributor.author | 江蕙妤 | zh_TW |
dc.date.accessioned | 2021-06-16T08:13:39Z | - |
dc.date.available | 2017-03-09 | |
dc.date.copyright | 2014-03-09 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-02-14 | |
dc.identifier.citation | Amina, R., Cheng, Y., Akhtar, H., Jean-Louis, M., 2013. Aptamers: a promising tool for ochratoxin A detection in food analysis. Toxins 2013.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/58395 | - |
dc.description.abstract | 經由系統配位子指數增益演繹程序(SELEX)篩選而得的適體長度通常介於60至120個鹼基之間,其中對標的物具有辨識能力的片段只占15至40個鹼基,此片段稱為微小適體。這些微小適體相較於全長適體除了具備更好的結合力和更快速的腎臟清除率之外,也大大降低了生產成本。本研究利用電腦模擬方法預測標的蛋白與其人工適體所形成之複合物構型,並進一步分析可能的微小適體序列。此微小適體預測程序應用於五條經實驗驗證的序列上,預測準確率可達0.92,顯示此程序在微小化適體研究上具有相當的潛力。本研究也利用相同程序針對自行篩選而得的H1N1流感病毒人工適體進行微小化,H1N1病毒中和試驗結果顯示,微小化適體之病毒中和能力相較於全長適體有顯著的提升,平均可達2.1倍,其中人工適體BR92在微小化後可使細胞存活率提高至98%,約為全長適體的3.4 倍。此外,分子嵌合結果顯示,利用唾液酸進行競爭式篩選所得的人工適體傾向結合於血球凝集素之第一結構域(HA1 domain),酵素結合適體分析(enzyme-linked aptamer assay, ELAA)也證實其對血球凝集素重組蛋白的專一性。本研究所提出之電腦模擬微小化適體方法可用於預測可能的微小適體參考序列,未來透過更多適體資料的蒐集可進一步進行程序優化,提高預測準確度。 | zh_TW |
dc.description.abstract | Aptamers screened out from SELEX (systematic evolution of ligands by exponential enrichment) are generally 60 to 120 bases in length, and only a fragment, called mini-aptamer, containing 15 to 40 bases contributes to the specific binding activity. In this study, structures of the aptamer-protein complexes were predicted, and mini-aptamers were identified from the predicted structures of complexes. The accuracy of prediction was as high as 0.92 when applying the pipeline to five verified aptamers. The result suggests that this pipeline is a potential tool for minimization of aptamers. The same pipeline was used to predict mini-aptamers from H1N1 aptamers obtained by viral SELEX. Compared to the full-length aptamers, mini-aptamers showed 2.1-fold improvement in viral neutralization test in average. Among these aptamers, viral neutralization test using truncated BR92 resulted in 98% of cell viability, which is 3.4-fold higher than full-length BR92. Furthermore, the docking results provided evidences that aptamers screened out by sialyllactose competitive selection tended to bind to the HA1 domain on hemagglutinin, and enzyme-linked aptamer assay (ELAA) also proved that these aptamers do specifically bind to hemagglutinin recombinant protein. In silico aptamer minimization pipeline proposed in this thesis provides a novel method to predict possible mini-aptamer sequences. Optimization of the pipeline can be done to enhance the prediction performer by introducing more aptamer database in the future. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T08:13:39Z (GMT). No. of bitstreams: 1 ntu-103-R00631048-1.pdf: 6660500 bytes, checksum: 0efd83221b33eba0953b345d1599e42b (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 誌謝 i
摘要 iii Abstract iv Content v List of Figures viii List of Tables x Chapter 1 Introduction 1 1.1 Motivation and objectives of this thesis 1 1.2 Strategy of this thesis 5 Chapter 2 Literature Review 7 2.1 Aptamers and SELEX technology 7 2.2 Post-SELEX optimization 8 2.3 Structural prediction of nucleic acid 11 2.4 Biomolecule docking 14 2.5 Human influenza 15 Chapter 3 Materials and Methods 22 3.1 Apparatus, reagents and software 22 3.2 Cell-based viral SELEX 25 3.3 In silico prediction of aptamers’ secondary structure 31 3.3.1 Secondary structure predicted by RNAStructure 31 3.3.2 Secondary structure predicted by software mfold 33 3.3.3 Format convertion from connectivity table to dot-bracket 34 3.4 In silico prediction of aptamers’ tertiary structure 35 3.4.1 Tertiary structure predicted by RNAcomposer 36 3.4.2 Tertiary structure predicted by iFoldRNA 36 3.4.3 Base mutation to replace Us by Ts 39 3.5 Molecule docking between hemagglutinin H1 and aptamers 40 3.5.1 Protein structure pre-processing 41 3.5.2 Protein-aptamer docking by PatchDock 41 3.6 Minimized aptamer sequences prediction 42 3.7 Aptamer microarray 45 3.8 Characterization of full-length and minimized H1N1 aptamers 46 3.8.1 Enzyme-linked aptamer assay 47 3.8.2 Hemagglutination inhibition assay 49 3.8.3 Viral neutralization test 50 3.8.4 Circular dichroism (CD) measurement 51 Chapter 4 Results and Discussion 52 4.1 Results of cell-SELEX against H1N1 virus 52 4.2 Validation of in silico aptamer minimization pipeline 54 4.3 Motif discovery by MAGIIC-PRO (CP9P dataset) 59 4.4 In silico hemagglutinin-aptamer docking 63 4.5 In silico minimization of H1N1 aptamers 67 4.6 Aptamer microarray for H1N1 aptamer candidates 72 4.7 Characterization of full-length and minimized aptamers 74 4.7.1 Enzyme-linked aptamer assay 74 4.7.2 Hemagglutination inhibition assay 77 4.7.3 Viral neutralization test 79 4.7.4 Circular dichroism of H1N1 aptamers 85 Chapter 5 Conclusion 88 Chapter 6 Suggestion 90 References 91 Appendix 100 | |
dc.language.iso | en | |
dc.title | 以分子嵌合軟體輔助H1N1流感病毒DNA適體篩選後微小化之研究 | zh_TW |
dc.title | Study of Docking-based In silico Post-SELEX Minimization for H1N1 Influenza DNA Aptamers | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳林祈(Lin-Chi Chen),劉?睿(Je-Ruei Liu),周崇熙(Chung-Hsi Chou),徐駿森(Chun-Hua Hsu) | |
dc.subject.keyword | 核酸適體,微小化,電腦模擬,分子嵌合,H1N1流感病毒, | zh_TW |
dc.subject.keyword | aptamer,minimization,in silico,molecule docking,H1N1 virus, | en |
dc.relation.page | 113 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-02-14 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 生物產業機電工程學研究所 | zh_TW |
顯示於系所單位: | 生物機電工程學系 |
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