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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 王勝仕 | |
dc.contributor.author | Hsiang-Chun Hsiao | en |
dc.contributor.author | 蕭翔駿 | zh_TW |
dc.date.accessioned | 2021-06-16T23:19:54Z | - |
dc.date.available | 2017-08-28 | |
dc.date.copyright | 2012-08-28 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-08-01 | |
dc.identifier.citation | [1] A. Surguchev and A. Surguchov, 'Conformational diseases: looking into the eyes,' Brain Res Bull, vol. 81, 12-24, 2010.
[2] L. Guo, T. E. Salt, V. Luong, N. Wood, W. Cheung, A. Maass, G. Ferrari, F. Russo-Marie, A. M. Sillito, M. E. Cheetham, S. E. Moss, F. W. Fitzke, and M. F. Cordeiro, 'Targeting amyloid-beta in glaucoma treatment,' Proc Natl Acad Sci U S A, vol. 104, 13444-9, 2007. [3] D. Pascolini and S. P. Mariotti, 'Global estimates of visual impairment: 2010,' British Journal of Ophthalmology, vol. 96, 614-618, 2012. [4] M. S. Kosinski-Collins and J. King, 'In vitro unfolding, refolding, and polymerization of human gamma D crystallin, a protein involved in cataract formation,' Protein Science, vol. 12, 480-490, 2003. [5] S. L. Flaugh, M. S. Kosinski-Collins, and J. King, 'Interdomain side-chain interactions in human gamma D crystallin influencing folding and stability,' Protein Science, vol. 14, 2030-2043, 2005. [6] I. A. Mills, S. L. Flaugh, M. S. Kosinski-Collins, and J. A. King, 'Folding and stability of the isolated Greek key domains of the long-lived human lens proteins gamma D-crystallin and gamma S-crystallin,' Protein Science, vol. 16, 2427-2444, 2007. [7] C. W. Oyster, The human eye, New ed.: Sinauer Associates Incorporated, 1999. [8] P. W. V. Gurney, 'Is our 'inverted' retina really 'bad design'? ,' Journal of Creation, vol. 13, 37-44, 1999. [9] K. H. Baratz, D. T. Gray, D. O. Hodge, L. C. Butterfield, and D. M. Ilstrup, 'Cataract extraction rates in Olmsted County, Minnesota, 1980 through 1994,' Archives of Ophthalmology, vol. 115, 1441-1446, 1997. [10] P. G. Montan, G. R. Koranyi, H. E. Setterquist, A. Stridh, B. T. Philipson, and K. Wiklund, 'Endophthalmitis after cataract surgery: Risk factors relating to technique and events of the operation and patient history - A retrospective case-control study,' Ophthalmology, vol. 105, 2171-2177, 1998. [11] T. Oshika, S. Amano, M. Araie, Y. Majima, and D. V. Leaming, 'Current trends in cataract and refractive surgery in Japan: 1998 survey,' Japanese Journal of Ophthalmology, vol. 44, 268-276, 2000. [12] T. Y. Wong and S. P. Chee, 'Risk factors of acute endophthalmitis after cataract extraction: a case-control study in Asian eyes,' British Journal of Ophthalmology, vol. 88, 29-31, 2004. [13] R. Klein, B. E. K. Klein, S. E. Moss, and K. L. P. Linton, 'The beaver dam eye study - Retinopathy in adults with newly discovered and previously diagnosed diabetes-Mellitus,' Ophthalmology, vol. 99, 58-62, 1992. [14] Lens and cataract 2001/2002 (Basic & Clinical Science Course): American Academy of Ophthalmology, 2001. [15] G. J. Johnson, The epidemiology of eye disease. London: Arnold, 2003. [16] C. W. Oyster. (1999). Cataracts. Available: http://www.photobiology.info/ [17] P. A. Asbell, L. Dualan, J. Mindel, D. Brocks, M. Ahmad, and S. Epstein, 'Age-related cataract,' Lancet, vol. 365, 599-609, 2005. [18] D. C. Beebe, N. M. Holekamp, and Y. B. Shui, 'Oxidative damage and the prevention of age-related cataracts,' Ophthalmic Research, vol. 44, 155-165, 2010. [19] J. R. Thompson, J. M. Sparrow, J. M. Gibson, and A. R. Rosenthal, 'Cataract and survival in an elderly nondiabetic population,' Arch Ophthalmol, vol. 111, 675-679, 1993. [20] S. S. S. Wang and W. S. Wen, 'Examining the influence of ultraviolet C irradiation on recombinant human gamma D-crystallin,' Molecular Vision, vol. 16, 2777-2790, 2010. [21] S. K. West, 'The epidemiology of cataract,' in Encyclopedia of the Eye, A. D. Editor-in-Chief: Darlene, Ed., ed Oxford: Academic Press, 2010, pp. 76-81. [22] G. M. Allardice, E. M. Wright, M. Peterson, and J. M. Miller, 'A statistical approach to an outbreak of endophthalmitis following cataract surgery at a hospital in the West of Scotland,' J Hosp Infect, vol. 49, 23-29, 2001. [23] I. G. Obrosova, S. S. M. Chung, and P. F. Kador, 'Diabetic cataracts: mechanisms and management,' Diabetes-Metabolism Research and Reviews, vol. 26, 172-180, 2010. [24] V. J. Stevens, C. A. Rouzer, V. M. Monnier, and A. Cerami, 'Diabetic cataract formation - Potential role of glycosylation of lens crystallins,' Proceedings of the National Academy of Sciences of the United States of America, vol. 75, 2918-2922, 1978. [25] A. I. Jobling and R. C. Augusteyn, 'What causes steroid cataracts? A review of steroid-induced posterior subcapsular cataracts,' Clinical and Experimental Optometry, vol. 85, 61-75, 2002. [26] K. M. Davenport and A. A. Patel, 'Cataracts,' Pediatr Rev, vol. 32, 82-83, 2011. [27] M. M. Deguti, U. J. Tietge, E. R. Barbosa, and E. L. Cancado, 'The eye in Wilson's disease: sunflower cataract associated with Kayser-Fleischer ring,' J Hepatol, vol. 37, 700, 2002. [28] V. Goyal and M. Tripathi, 'Sunflower cataract in Wilson's disease,' J Neurol Neurosurg Psychiatry, vol. 69, 133, 2000. [29] G. C. Robinson, J. E. Jan, and C. Kinnis, 'Congenital ocular blindness in children, 1945 to 1984,' American Journal of Diseases of Children, vol. 141, 1321-1324, 1987. [30] J. Graw, 'Congenital hereditary cataracts,' Int J Dev Biol, vol. 48, 1031-1044, 2004. [31] R. E. Bernstein, 'Nonenzymatically glycosylated proteins,' Advances in Clinical Chemistry, vol. 26, 1-78, 1987. [32] D. Goodsell. (2010). Crystallins. Available: http://www.rcsb.org/pdb/101/motm.do?momID=127 [33] J. Horwitz, 'Alpha-crystallin can function as a molecular chaperone,' Proceedings of the National Academy of Sciences of the United States of America, vol. 89, 10449-10453, 1992. [34] H. Bloemendal and W. W. Dejong, 'Lens proteins and their genes,' Progress in Nucleic Acid Research and Molecular Biology, vol. 41, 259-281, 1991. [35] W. W. de Jong, G. J. Caspers, and J. A. M. Leunissen, 'Genealogy of the alpha-crystallin - small heat-shock protein superfamily,' International Journal of Biological Macromolecules, vol. 22, 151-162, 1998. [36] T. Iwaki, A. Kumeiwaki, and J. E. Goldman, 'Cellular-distribution of Alpha-B-crystallin in non-lenticular tissues,' Journal of Histochemistry & Cytochemistry, vol. 38, 31-39, 1990. [37] A. N. Srinivasan, C. N. Nagineni, and S. P. Bhat, 'Alpha-a-Crystallin Is Expressed in Nonocular Tissues,' Journal of Biological Chemistry, vol. 267, 23337-23341, 1992. [38] T. H. MacRae, 'Structure and function of small heat shock/alpha-crystallin proteins: established concepts and emerging ideas,' Cell Mol Life Sci, vol. 57, 899-913, 2000. [39] J. Rozyczka and A. Gutsze, 'IR spectra of lens crystallins,' Lens Eye Toxic Res, vol. 8, 217-228, 1991. [40] L. Acosta-Sampson and J. King, 'Partially folded aggregation intermediates of human yD-, yC-, and yS-crystallin are recognized and bound by human alpha B-Crystallin chaperone,' Journal of Molecular Biology, vol. 401, 134-152, 2010. [41] J. N. Liang and X. Y. Li, 'Interaction and aggregation of lens crystallins,' Experimental Eye Research, vol. 53, 61-66, 1991. [42] J. Horwitz, 'The function of alpha-crystallin in vision,' Semin Cell Dev Biol, vol. 11, 53-60, 2000. [43] L. I. Acosta Sampson, S. Flaugh, I. Milis, and J. King, 'Human alpha-crystallin chaperone suppresses the aggregation of partially folded intermediates of human gamma D-crystallin and its deamidated forms.,' Faseb Journal, vol. 21, A1025-A1025, 2007. [44] J. D. Gunton, A. Shiryayev, and D. L. Pagan, Protein condensation : kinetic pathways to crystallization and disease. New York: Cambridge University Press, 2007. [45] H. Bloemendal, W. de Jong, R. Jaenicke, N. H. Lubsen, C. Slingsby, and A. Tardieu, 'Ageing and vision: structure, stability and function of lens crystallins,' Prog Biophys Mol Biol, vol. 86, 407-485, 2004. [46] S. Zarina, C. Slingsby, R. Jaenicke, Z. H. Zaidi, H. Driessen, and N. Srinivasan, 'Three-dimensional model and quaternary structure of the human eye lens protein gamma S-crystallin based on beta- and gamma-crystallin X-ray coordinates and ultracentrifugation,' Protein Sci, vol. 3, 1840-1846, 1994. [47] R. Jaenicke and C. Slingsby, 'Lens crystallins and their microbial homologs: structure, stability, and function,' Crit Rev Biochem Mol Biol, vol. 36, 435-499, 2001. [48] S. R. Hanson, D. L. Smith, and J. B. Smith, 'Deamidation and disulfide bonding in human lens gamma-crystallins,' Experimental Eye Research, vol. 67, 301-312, 1998. [49] R. H. Brakenhoff, H. J. Aarts, F. H. Reek, N. H. Lubsen, and J. G. Schoenmakers, 'Human gamma-crystallin genes. A gene family on its way to extinction,' Journal of Molecular Biology, vol. 216, 519-532, 1990. [50] A. Laganowsky, C. Liu, M. R. Sawaya, J. P. Whitelegge, J. Park, M. Zhao, A. Pensalfini, A. B. Soriaga, M. Landau, P. K. Teng, D. Cascio, C. Glabe, and D. Eisenberg, 'Atomic view of a toxic amyloid small oligomer,' Science, vol. 335, 1228-1231, 2012. [51] E. M. Mayr, R. Jaenicke, and R. Glockshuber, 'Domain interactions and connecting peptides in lens crystallins,' Journal of Molecular Biology, vol. 235, 84-88, 1994. [52] S. L. Flaugh, M. S. Kosinski-Collins, and J. King, 'Contributions of hydrophobic domain interface interactions to the folding and stability of human gammaD-crystallin,' Protein Sci, vol. 14, 569-81, 2005. [53] P. Das, J. A. King, and R. H. Zhou, 'Beta-strand interactions at the domain interface critical for the stability of human lens gamma D-crystallin,' Protein Science, vol. 19, 131-140, 2010. [54] A. Basak, O. Bateman, C. Slingsby, A. Pande, N. Asherie, O. Ogun, G. B. Benedek, and J. Pande, 'High-resolution X-ray crystal structures of human gamma D crystallin (1.25 angstrom) and the R58H mutant (1.15 angstrom) associated with aculeiform cataract,' Journal of Molecular Biology, vol. 328, 1137-1147, 2003. [55] P. Evans, K. Wyatt, G. J. Wistow, O. A. Bateman, B. A. Wallace, and C. Slingsby, 'The P23T cataract mutation causes loss of solubility of folded gamma D-crystallin,' Journal of Molecular Biology, vol. 343, 435-444, 2004. [56] M. S. Kosinski-Collins, S. L. Flaugh, and J. King, 'Probing folding and fluorescence quenching in human gamma D crystallin Greek key domains using triple tryptophan mutant proteins,' Protein Science, vol. 13, 2223-2235, 2004. [57] A. Pande, O. Annunziata, N. Asherie, O. Ogun, G. B. Benedek, and J. Pande, 'Decrease in protein solubility and cataract formation caused by the Pro23 to Thr mutation in human gamma D-crystallin,' Biochemistry, vol. 44, 2491-2500, 2005. [58] S. L. Flaugh, M. S. Kosinski-Collins, and J. King, 'Contributions of hydrophobic domain interface interactions to the folding and stability of human gamma D-crystallin,' Protein Science, vol. 14, 571-581, 2005. [59] S. L. Flaugh, I. A. Mills, and J. King, 'Glutamine deamidation destabilizes human gamma D-crystallin and lowers the kinetic barrier to unfolding,' The Journal of Biological Chemistry, vol. 281, 30782-30793, 2006. [60] J. Jung, I. J. L. Byeon, Y. T. Wang, J. King, and A. M. Gronenborn, 'The structure of the cataract-causing P23T mutant of human gamma D-crystallin exhibits distinctive local conformational and dynamic changes,' Biochemistry, vol. 48, 2597-2609, 2009. [61] K. L. Moreau and J. King, 'Hydrophobic core mutations associated with cataract development in mice destabilize human gamma D-crystallin,' The Journal of Biological Chemistry, vol. 284, 33285-33295, 2009. [62] V. P. R. Vendra and D. Balasubramanian, 'Structural and aggregation behavior of the human gamma D-crystallin mutant E107A, associated with congenital nuclear cataract,' Molecular Vision, vol. 16, 2822-2828, 2010. [63] P. R. Banerjee, A. Pande, J. Patrosz, G. M. Thurston, and J. Pande, 'Cataract-associated mutant E107A of human gamma D-crystallin shows increased attraction to alpha-crystallin and enhanced light scattering,' Proceedings of the National Academy of Sciences of the United States of America, vol. 108, 574-579, 2011. [64] W. Zhang, H. C. Cai, F. F. Li, Y. B. Xi, X. Ma, and Y. B. Yan, 'The congenital cataract-linked G61C mutation destabilizes gamma D-crystallin and promotes non-native aggregation,' Plos One, vol. 6, 2011. [65] F. R. Kong and J. King, 'Contributions of aromatic pairs to the folding and stability of long-lived human gamma D-crystallin,' Protein Science, vol. 20, 513-528, 2011. [66] E. Sahin, J. L. Jordan, M. L. Spatara, A. Naranjo, J. A. Costanzo, W. F. Weiss, A. S. Robinson, E. J. Fernandez, and C. J. Roberts, 'Computational design and biophysical characterization of aggregation-resistant point mutations for gamma D crystallin illustrate a balance of conformational stability and intrinsic aggregation propensity,' Biochemistry, vol. 50, 628-639, 2011. [67] D. R. Goulet, K. M. Knee, and J. A. King, 'Inhibition of unfolding and aggregation of lens protein human gamma D crystallin by sodium citrate,' Experimental Eye Research, vol. 93, 371-381, 2011. [68] M. J. C. Crabbe, L. R. Cooper, and D. W. Corne, 'Use of essential and molecular dynamics to study γB-crystallin unfolding after non-enzymic post-translational modifications,' Computational Biology and Chemistry, vol. 27, 507-510, 2003. [69] J. T. MacDonald, A. G. Purkiss, M. A. Smith, P. Evans, J. M. Goodfellow, and C. Slingsby, 'Unfolding crystallins: the destabilizing role of a beta-hairpin cysteine in betaB2-crystallin by simulation and experiment,' Protein Sci, vol. 14, 1282-92, 2005. [70] J. J. Chen, S. L. Flaugh, P. R. Callis, and J. King, 'Mechanism of the highly efficient quenching of tryptophan fluorescence in human gamma D-crystallin,' Biochemistry, vol. 45, 11552-11563, 2006. [71] A. G. Purkiss, O. A. Bateman, K. Wyatt, P. A. Wilmarth, L. L. David, G. J. Wistow, and C. Slingsby, 'Biophysical properties of gammaC-crystallin in human and mouse eye lens: the role of molecular dipoles,' Journal of Molecular Biology, vol. 372, 205-22, 2007. [72] M. Michiel, F. Skouri-Panet, E. Duprat, S. Simon, C. Ferard, A. Tardieu, and S. Finet, 'Abnormal assemblies and subunit exchange of alphaB-crystallin R120 mutants could be associated with destabilization of the dimeric substructure,' Biochemistry, vol. 48, 442-53, 2009. [73] A. Pande, J. C. Zhang, P. R. Banerjee, S. S. Puttamadappa, A. Shekhtman, and J. Pande, 'NMR study of the cataract-linked P23T mutant of human gamma D-crystallin shows minor changes in hydrophobic patches that reflect its retrograde solubility,' Biochemical and Biophysical Research Communications, vol. 382, 196-199, 2009. [74] P. Das, J. A. King, and R. Zhou, 'Aggregation of gamma-crystallins associated with human cataracts via domain swapping at the C-terminal beta-strands,' Proc Natl Acad Sci U S A, vol. 108, 10514-9, 2011. [75] D. van der Spoel, P. J. van Maaren, and C. Caleman, 'GROMACS molecule & liquid database,' Bioinformatics, vol. 28, 752-3, 2012. [76] D. Sellis, D. Vlachakis, and M. Vlassi, 'Gromita: a fully integrated graphical user interface to gromacs 4,' Bioinform Biol Insights, vol. 3, 99-102, 2009. [77] D. Van Der Spoel, E. Lindahl, B. Hess, G. Groenhof, A. E. Mark, and H. J. Berendsen, 'GROMACS: fast, flexible, and free,' Journal of Computational Chemistry, vol. 26, 1701-18, 2005. [78] (2007). GNU general public license. Available: http://www.gnu.org/licenses/gpl.html [79] S. Le Roux and V. Petkov, 'ISAACS - interactive structure analysis of amorphous and crystalline systems,' Journal of Applied Crystallography, vol. 43, 181-185, 2010. [80] B. Hess, H. Bekker, H. J. C. Berendsen, and J. Fraaije, 'LINCS: A linear constraint solver for molecular simulations,' Journal of Computational Chemistry, vol. 18, 1463-1472, 1997. [81] K.-C. Lin, ' Effects of phospholipids on the aggregation behaviors of β-amyloid peptide and its mutant,' Master, National Taiwan University, 2010. [82] T. Darden, D. York, and L. Pedersen, 'Particle mesh ewald - An n.log(N) method for ewald sums in large systems,' Journal of Chemical Physics, vol. 98, 10089-10092, 1993. [83] U. Essmann, L. Perera, M. L. Berkowitz, T. Darden, H. Lee, and L. G. Pedersen, 'A smooth particle mesh ewald method,' Journal of Chemical Physics, vol. 103, 8577-8593, 1995. [84] N. Michaud-Agrawal, E. J. Denning, T. B. Woolf, and O. Beckstein, 'MDAnalysis: A toolkit for the analysis of molecular dynamics simulations,' Journal of Computational Chemistry, 2011. [85] W. Kabsch and C. Sander, 'Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features,' Biopolymers, vol. 22, 2577-2637, 1983. [86] Y. T. Wang, S. Petty, A. Trojanowski, K. Knee, D. Goulet, I. Mukerji, and J. King, 'Formation of amyloid fibrils in vitro from partially unfolded intermediates of human gamma C-crystallin,' Investigative Ophthalmology and Visual Science, vol. 51, 672-678, 2010. [87] M. Frigo and S. G. Johnson, 'The design and implementation of FFTW3,' Proceedings of the Ieee, vol. 93, 216-231, 2005. [88] M. J. Abraham and J. E. Gready, 'Optimization of Parameters for Molecular Dynamics Simulation Using Smooth Particle-Mesh Ewald in GROMACS 4.5,' Journal of Computational Chemistry, vol. 32, 2031-2040, 2011. [89] B. Hess, C. Kutzner, D. van der Spoel, and E. Lindahl, 'GROMACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation,' Journal of Chemical Theory and Computation, vol. 4, 435-447, 2008. [90] W. Humphrey, A. Dalke, and K. Schulten, 'VMD: Visual molecular dynamics,' Journal of Molecular Graphics & Modelling, vol. 14, 33-38, 1996. [91] A. J. Maynard, T. Ehlers, and J. Koska, 'Docking and scoring in Discovery Studio,' Abstracts of Papers of the American Chemical Society, vol. 241, 2011. [92] W. Kabsch and C. Sander, 'Dictionary of Protein Secondary Structure - Pattern-Recognition of Hydrogen-Bonded and Geometrical Features,' Biopolymers, vol. 22, 2577-2637, 1983. [93] B. d. Groot. (2008). Introduction to protein simulation. Available: http://www3.mpibpc.mpg.de/groups/de_groot/index.html [94] M. Vendruscolo and E. Domany, 'Protein folding using contact maps,' Vitam Horm, vol. 58, 171-212, 2000. [95] C. Vehlow, H. Stehr, M. Winkelmann, J. M. Duarte, L. Petzold, J. Dinse, and M. Lappe, 'CMView: interactive contact map visualization and analysis,' Bioinformatics, vol. 27, 1573-4, 2011. [96] Y. Ye and A. Godzik, 'Multiple flexible structure alignment using partial order graphs,' Bioinformatics, vol. 21, 2362-9, 2005. [97] A. M. Bonvin and W. F. van Gunsteren, 'Beta-hairpin stability and folding: molecular dynamics studies of the first beta-hairpin of tendamistat,' Journal of Molecular Biology, vol. 296, 255-68, 2000. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65062 | - |
dc.description.abstract | 白內障是一種發生於眼睛水晶體的疾病,當其呈現混濁,造成視力上的障礙時,稱為白內障。一般而言,白內障主要的成因主要是由於水晶體中的蛋白質變性,而導致形成不可溶的聚集體,進而影響水晶體之透明度。
人類γD型水晶體蛋白(human γD crystalline(HGDC))為一由173個胺基酸所組成的蛋白質,是人類γ型水晶體主要蛋白質成份之一。本研究是使用分子模擬的方式,將HGDC分別置於中性(pH 7)與酸性(pH 2)的環境條件下進行模擬,並嘗試使用高溫的方式提高分子動能加速其反應,並藉由RMSD(root mean square deviation)、Native contact、Contact map等方式進行探討,探討環境因子對HGDC結構穩定性的影響,並且推測其可能的分子機制。 由分子模擬的結果可以得到以下的結論,HGDC於酸性(pH 2)鹽溶液的條件下,其整體結構上較HGDC於中性(pH 7)鹽溶液中者來得不穩定;並且發現HGDC interface之殘基(M43, F56, I81, V132, L145, V170, Q54, Q143, R79 and M147)於pH 2的條件下較pH 7易失去其Native contact。此外,當提高模擬溫度進行分子模擬時,發現pH 2 HGDC之interface會於分子模擬中早期失去Native contact,連帶影響HGDC之N-motif2的穩定性。由於HGDC之N-motif2被interface影響,導致其N-domain呈現結構變化較大,較易去折疊;將分子模擬之結果進行疊圖可發現當HGDC去折疊時,會由domain以一前一後的方式展開其interface而使其失去Native contact。我們期望藉由本研究能對於白內障之發生機制有進一步之瞭解。 | zh_TW |
dc.description.abstract | Cataract is a clouding that develops in the crystalline lens of the eye. It is commonly believed to be caused by the aggregation of partially unfolded lens crystallin proteins, thereby affecting the transparency of the lens.
Human γD-crystallin, a 173 amino acid protein, is a primary protein component of human γ crystallin protein. In the thesis, we use molecular dynamic simulations to investigate the unfolding mechanisms of human γD-crystallin at pH 2.0 and pH 7.0. Analyses including root mean square deviation (RMSD), native contact and contact map are performed to provide the stability information of human γD-crystallin at different conditions, and speculate the possible mechanism. Our simulations results showed that human γD-crystallin is more unstable in the acidic condition (pH 2.0) as compared to the neutral pH condition (pH 7.0). In addition, we found that the interface residues of human γD-crystallin (M43, F56, I81, V132, L145, V170, Q54, Q143, R79 and M147) are prone to lose their native contact in the acid condition. In addition, as molecular dynamic simulations conducted at higher temperatures, we noticed that the native contact of human γD-crystallin’s interface was lost at an early simulation time, thus affecting the stability of motif2 at the N-domain. Therefore, human γD-crystallin N-domain has larger changes in its structure and unfolds easily. Moreover, through superimposition, we observed that human γD-crystallin unfolds by twisting its N-domain and C-domain. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T23:19:54Z (GMT). No. of bitstreams: 1 ntu-101-R99524009-1.pdf: 19814408 bytes, checksum: 43720cabb880c98a611da196c900b933 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 目錄
口試委員會審定書 I 誌謝 II 中文摘要 III Abstract IV 圖目錄 X 表目錄 XIV 第一章 緒論 1 第二章 文獻回顧 2 2-1 白內障相關研究 2 2-2 水晶體蛋白簡介 9 2-2-1 α-crystallin 10 2-2-2 βγ-crystallin 11 2-2-3 Human γD crystalline 14 2-3 分子模擬簡介 26 2-3-1 GROMACS 26 2-3-2 Root mean square deviation(RMSD)分析法 30 2-3-3 Native contact 31 2-4 其他分子模擬相關程式簡介 32 2-4-1 Dictionary of Protein Secondary Structure 32 2-4-2 MDAnalysis 35 第三章 研究動機 36 第四章 實驗儀器與步驟 37 4-1 實驗儀器與軟體 37 4-2 軟體安裝與設定 38 4-2-1 Ubuntu安裝 38 4-2-2 GROMACS安裝 41 4-2-3 MDAnalysis安裝 44 4-2-4 VMD安裝 45 4-3 分子模擬系統之建構與步驟 46 4-3-1 操作步驟(以在 pH 2之HGDC為例) 47 4-3-2 分子動態模擬參數設定 50 第五章 實驗結果與討論 52 5-1 在310K下不同pH值對於HGDC結構之影響 52 5-1-1 HGDC穩定度分析 53 5-1-2 HGDC Interface Contact Map分析 57 5-2 在343K下不同pH值對於HGDC結構之影響 63 5-2-1 HGDC穩定度分析 64 5-2-2 DSSP(Dictionary of protein secondary structure)圖分析 68 5-2-3 HGDC之interface分析 70 5-3 在380K下不同pH值對於HGDC結構之影響 76 5-3-1 HGDC穩定度分析 77 5-3-2 DSSP(Dictionary of protein secondary structure)圖分析 81 5-3-3 HGDC之interface分析 83 第六章 結論與建議 88 6-1 實驗結論 88 6-2 建議與未來展望 90 參考資料 91 附錄 99 附錄A、GROMACS calculation 99 i. RMSD method 99 ii. Solvent accessible surface area計算 101 iii. 分組做法: 103 iv. 分子(或原子)間質心距離的計算方式 105 v. Radius of gyration 106 vi. Energy calculation 107 vii. Do_DSSP 108 附錄B、MDAnalysis 111 i. Native Contact for all protein (Ca) 111 ii. Native contact for part of system and contact map 112 iii. Subtraction contact map 118 附錄 C、其他程式 123 i. DSSP Figure繪製方式 123 ii. PIC: Protein interaction calculator 126 iii. PPI-Pred: Protein-Protein Interface Prediction 128 iv. POPS 130 v. Superimposition 132 附錄D、Cloning of HGDC 133 i. PCR 133 ii. Restriction Enzyme Reaction Results 135 iii. Ligation 136 iv. Transformation (CaCl2) 137 附錄 E、HGDC alignment 139 Alignment步驟與方法: 139 310K alignment 140 343K alignment 148 380K alignment 158 solvent accessible surface area 分析 170 附錄F、VMD動畫製作 172 附錄G、檔案對照表 178 | |
dc.language.iso | zh-TW | |
dc.title | 探討人類水晶體蛋白之聚集行為 | zh_TW |
dc.title | Exploring the Aggregation Behaviors of Human γD Cryastallin Proteins | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林達顯,林錕松,王孟菊,詹正雄 | |
dc.subject.keyword | 白內障,人類水晶體蛋白,分子動力學模擬,蛋白質折疊/去折疊機制,contact map, | zh_TW |
dc.subject.keyword | cataract,human cryastallin,molecular dynamic simulation,protein folding/unfolding,contact map, | en |
dc.relation.page | 181 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-08-01 | |
dc.contributor.author-college | 工學院 | zh_TW |
dc.contributor.author-dept | 化學工程學研究所 | zh_TW |
顯示於系所單位: | 化學工程學系 |
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