類澱粉胜肽聚集行為之電腦模擬

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姓名

張育維(Yu-Wei Chang) 查詢紙本館藏

畢業系所

化學工程與材料工程學系

論文名稱

類澱粉胜肽聚集行為之電腦模擬
(Aggregation and Membrane Interactions of Amyloid b Peptides Fragments (16-22 & 25-35) in Water-Membrane Environment Studied by Molecular Dynamics Simulations)

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摘要(中)

本論文利用最新發展的implicit solvent/membrane模型，配合定溫分子動態法及變溫replica exchange分子動態法模擬Ab16-22及Ab25-35胜肽鏈在水相中及有膜存在的環境下，其聚集及吸附的機制，以期了解全長Ab1-40/42的細胞毒性機制。此ㄧ方法可改善全原子模型計算時間不足的問題，進而使模擬的時間尺度更能逼近實驗的條件，且藉由從原子及動態的時間角度出發，可彌補實驗上不易觀察到的現象。
由於Ab16-22(較具疏水性)與Ab25-35(兩性性質)基本性質不同，表現出的聚集及吸附行為也不同：Ab16-22胜肽鏈傾向於在水相中先行聚集而成寡聚物，而後再逐漸吸附到膜面上；然而，Ab25-35胜肽鏈傾向以單體的形態先吸附到膜面上，吸附上膜面的單體在膜面上互相聚集形成寡聚物；在水相中，Ab16-22胜肽鏈傾向形成b-sheet二級結構，Ab25-35胜肽鏈則傾向形成helix結構；在膜面上的結構與水相中不同，Ab16-22胜肽鏈在膜面上傾向形成helix，而Ab25-35胜肽鏈則表現出較多樣的結構形態，包含形成在C端的helix結構。雖然Ab16-22及Ab25-35兩者的聚集及吸附表現不同，但其聚集及吸附的主要交互作用力卻相似：兩者聚集主要是以疏水作用力為主，而寡聚物吸附到膜面上則是以靜電作用力為主。
本研究從原子尺度了解Ab的聚集及吸附的機制，可提供我們一個理論基礎，以合理設計相關的治療藥物，以抑制Ab細胞毒性的產生。

摘要(英)

This study employed the constant temperature molecular dynamics and replica-exchange molecular dynamics in terms of the recently developed implicit solvent and membrane models to simulate the aggregation and adsorption mechanisms of the Ab16-22 and Ab25-35 peptide in the present of membrane. This study is motivated to understand the toxic mechanism of full-length Ab1-40/1-42. Our method improves the time-consuming problem of all-atom simulations and will approach the experimental time scale. In views of atomic and fast time scales, our results complement the intermediate processes which were difficult to be observed experimentally.
Due to the different properties of Ab16-22 and Ab25-35 peptides in which they are hydrophobic and amphiphilic, respectively, their mechanisms of aggregation and adsorption are also different: Ab16-22 peptides are prone to aggregate in water phase, and then to be adsorbed to membrane; In contrast, Ab25-35 peptides trends to be adsorbed on membrane in the monomer form, then, the monomers are to be aggregated on membrane. In water phase, Ab16-22 peptides prefer to form b-sheet secondary structure and the Ab25-35 peptides form helix secondary structure. In membrane phase, Ab16-22 peptides prefer to form helix secondary structure. The secondary structures of Ab25-35 peptides in membrane are more diverse. If the helix secondary structure of Ab25-35 peptides is formed, it exists in the C-terminal. Although the aggregation and adsorption mechanisms are different for Ab16-22 and Ab25-35 peptides, they shares similar interactions: For aggregation, the interactions are mainly dominated by hydrophobic effect; for adsorption, it is driven by electrostatics interactions.
This study understands the mechanisms of Ab aggregation and adsorption in atomic and fast time scales proving us a theoretical guideline for rational drug design to inhibit the cell toxicity of amyloid.

關鍵字(中)

★ 分子動態模擬
★ 類澱粉胜肽

關鍵字(英)

★ molecular dynamics simulations
★ beta amyloid

論文目次

中文摘要 I
Abstract II
目錄 III
圖目錄 V
表目錄 X
第一章序論 1
第二章文獻回顧 2
2.1 前言 2
2.2 蛋白質的摺疊之原理及機制 3
2.3 蛋白質錯誤摺疊、聚集及類澱粉蛋白纖維之生成 5
2.4 阿茲海默症(Alzheimer’s Disease，AD) 7
2.5 類澱粉胜肽(b-Amyloid，Ab) 9
2.6 類澱粉胜肽纖維分子結構 10
2.6.1 固態核磁共振 11
2.6.2 電子自旋共振(EPR) 13
2.6.3 X-Ray散射 13
2.7 類澱粉胜肽纖維形成之巨觀機制 14
2.8 分子動態法模擬類澱粉胜肽之聚集 15
第三章方法與原理 18
3.1 簡介 18
3.2 分子力場(Force Field) 19
3.2.1 鍵伸縮位能 20
3.2.2 鍵彎曲位能 20
3.2.3 鍵角扭曲位能 21
3.2.4 不規則鍵角扭曲位能 21
3.2.5 凡得瓦作用力 22
3.2.6 庫倫靜電作用力 23
3.3 基本動力原理 24
3.4 週期性邊界條件(Periodic Boundary Conditions, PBC) 25
3.5 Generalized Born Solvent Model (GB Model) 27
3.6 Replica-Exchange Molecular Dynamics Method (REMD) 31
3.7 Dictionary of Secondary Structure of Proteins (DSSP) 37
3.8 分子動態模擬系統與條件、方法介紹 40
3.8.1 主要模擬分子 41
3.8.2 系統概述： 41
第四章結果與討論 43
4.1 Ab16-22聚集及吸附行為的探討 44
4.1.1 Ab16-22胜肽鏈與膜的交互作用機制 44
4.1.2 Ab16-22在水相中的聚集 84
4.2 Ab25-35聚集及吸附行為的探討 91
4.2.1 Ab25-35胜肽鏈聚集及吸附到膜面的機制 91
4.2.2 Ab25-35胜肽鏈的二級結構 112
4.2.3 Ab25-35在水相中的聚集 123
第五章結論 127
第六章參考文獻 129

參考文獻

1 McLean, C. A., R. A. Cherny, F. W. Fraser, S. J. Fuller, M. J. Smith, K. Beyreuther, A. I. Bush and C. L. Masters (1999) Soluble pool of A beta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Annals of Neurology. 46, 860-866.
2 Rosenblum, W. I. (2002) Structure and location of amyloid beta peptide chains and arrays in Alzheimer's disease: New findings require reevaluation of the amyloid hypothesis and of tests of the hypothesis. Neurobiology of Aging. 23, 225-230.
3 Walsh, D. M., I. Klyubin, J. V. Fadeeva, W. K. Cullen, R. Anwyl, M. S. Wolfe, M. J. Rowan and D. J. Selkoe (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature. 416, 535-539.
4 Armen, R. S., M. L. DeMarco, D. O. V. Alonso and V. Daggett (2004) Pauling and Corey's alpha-pleated sheet structure may define the prefibrillar amyloidogenic intermediate in amyloid disease. Proceedings of the National Academy of Sciences of the United States of America. 101, 11622-11627.
5 Bernstein, S. L., T. Wyttenbach, A. Baumketner, J. E. Shea, G. Bitan, D. B. Teplow and M. T. Bowers (2005) Amyloid beta-protein: Monomer structure and early aggregation states of A beta 42 and its Pro(19) alloform. Journal of the American Chemical Society. 127, 2075-2084.
6 Borreguero, J. M., B. Urbanc, N. D. Lazo, S. V. Buldyrev, D. B. Teplow and H. E. Stanley (2005) Folding events in the 21-30 region of amyloid-beta-protein (A beta) studied in silico. Proceedings of the National Academy of Sciences of the United States of America. 102, 6015-6020.
7 Dedmon, M. M., K. Lindorff-Larsen, J. Christodoulou, M. Vendruscolo and C. M. Dobson (2005) Mapping long-range interactions in alpha-synuclein using spin-label NMR and ensemble molecular dynamics simulations. Journal of the American Chemical Society. 127, 476-477.
8 Massi, F. and J. E. Straub (2003) Structural and dynamical analysis of the hydration of the Alzheimer's beta-amyloid peptide. Journal of Computational Chemistry. 24, 143-153.
9 Sgourakis, N. G., Y. L. Yan, S. A. McCallum, C. Y. Wang and A. E. Garcia (2007) The Alzheimer's peptides A beta 40 and 42 adopt distinct conformations in water: A combined MD/NMR study. Journal of Molecular Biology. 368, 1448-1457.
10 Barducci, A., R. Chelli, P. Procacci, V. Schettino, F. L. Gervasio and M. Parrinello (2006) Metadynamics simulation of prion protein: beta-structure stability and the early stages of misfolding. Journal of the American Chemical Society. 128, 2705-2710.
11 Han, W. and Y. D. Wu (2005) A strand-loop-strand structure is a possible intermediate in fibril elongation: Long time simulations of amylold-beta peptide (10-35). Journal of the American Chemical Society. 127, 15408-15416.
12 Haspel, N., D. Zanuy, B. Y. Ma, H. Wolfson and R. Nussinov (2005) A comparative study of amyloid fibril formation by residues 15-19 of the human calcitonin hormone: A single beta-sheet model with a small hydrophobic core. Journal of Molecular Biology. 345, 1213-1227.
13 Huet, A. and P. Derreumaux (2006) Impact of the mutation A21G (Flemish variant) on Alzheimer's beta-amyloid dimers by molecular dynamics simulations. Biophysical Journal. 91, 3829-3840.
14 Massi, F., D. Klimov, D. Thirumalai and J. E. Straub (2002) Charge states rather than propensity for beta-structure determine enhanced fibrillogenesis in wild-type Alzheimer's beta-amyloid peptide compared to E22Q Dutch mutant. Protein Science. 11, 1639-1647.
15 Klimov, D. K. and D. Thirumalai (2003) Dissecting the assembly of A beta(16-22) amyloid peptides into antiparallel beta sheets. Structure. 11, 295-307.
16 Melquiond, A., G. Boucher, N. Mousseau and P. Derreumaux (2005) Following the aggregation of amyloid-forming peptides by computer simulations. Journal of Chemical Physics. 122, -.
17 Paci, E., J. Gsponer, X. Salvatella and M. Vendruscolo (2004) Molecular dynamics studies of the process of amyloid aggregation of peptide fragments of transthyretin. Journal of Molecular Biology. 340, 555-569.
18 Santini, S., N. Mousseau and P. Derreumaux (2004) In silico assembly of Alzheimer's A beta(16-22) peptide into beta-sheets. Journal of the American Chemical Society. 126, 11509-11516.
19 Santini, S., G. H. Wei, N. Mousseau and P. Derreumaux (2004) Pathway complexity of Alzheimer's beta-amyloid A beta(16-22) peptide assembly. Structure. 12, 1245-1255.
20 Tarus, B., J. E. Straub and D. Thirumalai (2005) Probing the initial stage of aggregation of the A beta(10-35)-protein: Assessing the propensity for peptide dimerization. Journal of Molecular Biology. 345, 1141-1156.
21 Wei, G. H., N. Mousseau and P. Derreumaux (2004) Sampling the self-assembly pathways of KFFE hexamers. Biophysical Journal. 87, 3648-3656.
22 Wu, C., H. X. Lei and Y. Duan (2005) Elongation of ordered peptide aggregate of an amyloidogenic hexapeptide NFGAIL observed in molecular dynamics simulations with explicit solvent. Journal of the American Chemical Society. 127, 13530-13537.
23 Li, L. P., T. A. Darden, L. Bartolotti, D. Kominos and L. G. Pedersen (1999) An atomic model for the pleated beta-sheet structure of A beta amyloid protofilaments. Biophysical Journal. 76, 2871-2878.
24 Ma, B. Y. and R. Nussinov (2002) Stabilities and conformations of Alzheimer's beta-amyloid peptide oligomers (A beta(16-22 ') A beta(16-35 ') and A beta(10-35)): Sequence effects. Proceedings of the National Academy of Sciences of the United States of America. 99, 14126-14131.
25 Meinke, J. H. and U. H. E. Hansmann (2007) Aggregation of beta-amyloid fragments. Journal of Chemical Physics. 126, -.
26 Zanuy, D., K. Gunasekaran, B. Y. Ma, H. H. Tsai, C. J. Tsai and R. Nussinov (2004) Insights into amyloid structural formation and assembly through computational approaches. Amyloid-Journal of Protein Folding Disorders. 11, 143-161.
27 Hwang, W., S. G. Zhang, R. D. Kamm and M. Karplus (2004) Kinetic control of dimer structure formation in amyloid fibrillogenesis. Proceedings of the National Academy of Sciences of the United States of America. 101, 12916-12921.
28 Nguyen, H. D. and C. K. Hall (2005) Kinetics of fibril formation by polyalanine peptides. Journal of Biological Chemistry. 280, 9074-9082.
29 Baumketner, A. and J. E. Shea (2005) Free energy landscapes for amyloidogenic tetrapeptides dimerization. Biophysical Journal. 89, 1493-1503.
30 Cecchini, M., F. Rao, M. Seeber and A. Caflisch (2004) Replica exchange molecular dynamics simulations of amyloid peptide aggregation. Journal of Chemical Physics. 121, 10748-10756.
31 Favrin, G., A. Irback and S. Mohanty (2004) Oligomerization of amyloid A beta(16-22) peptides using hydrogen bonds and hydrophobicity forces. Biophysical Journal. 87, 3657-3664.
32 Gnanakaran, S., R. Nussinov and A. E. Garcia (2006) Atomic-level description of amyloid beta-dimer formation. Journal of the American Chemical Society. 128, 2158-2159.
33 Nguyen, H. D. and C. K. Hall (2006) Spontaneous fibril formation by polyalanines; Discontinuous molecular dynamics simulations. Journal of the American Chemical Society. 128, 1890-1901.
34 Tsai, H. H., M. Reches, C. J. Tsai, K. Gunasekaran, E. Gazit and R. Nussinov (2005) Energy landscape of amyloidogenic peptide oligomerization by parallel-tempering molecular dynamics simulation: Significant role of Asn ladder. Proceedings of the National Academy of Sciences of the United States of America. 102, 8174-8179.
35 Urbanc, B., L. Cruz, F. Ding, D. Sammond, S. Khare, S. V. Buldyrev, H. E. Stanley and N. V. Dokholyan (2004) Molecular dynamics simulation of amyloid beta dimer formation. Biophysical Journal. 87, 2310-2321.
36 Stefani, M. and C. M. Dobson (2003) Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution. Journal of Molecular Medicine-Jmm. 81, 678-699.
37 Dill, K. A. and H. S. Chan (1997) From Levinthal to pathways to funnels. Nature Structural Biology. 4, 10-19.
38 Wolynes, P. G., J. N. Onuchic and D. Thirumalai (1995) Navigating the Folding Routes. Science. 267, 1619-1620.
39 Vendruscolo, M., E. Paci, C. M. Dobson and M. Karplus (2001) Three key residues form a critical contact network in a protein folding transition state. Nature. 409, 641-645.
40 Hardy, J. and D. J. Selkoe (2002) Medicine - The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science. 297, 353-356.
41 Kayed, R., E. Head, J. L. Thompson, T. M. McIntire, S. C. Milton, C. W. Cotman and C. G. Glabe (2003) Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science. 300, 486-489.
42 Miller, D. L., I. A. Papayannopoulos, J. Styles, S. A. Bobin, Y. Y. Lin, K. Biemann and K. Iqbal (1993) Peptide Compositions of the Cerebrovascular and Senile Plaque Core Amyloid Deposits of Alzheimers-Disease. Arch Biochem Biophys. 301, 41-52.
43 Lambert, M. P., A. K. Barlow, B. A. Chromy, C. Edwards, R. Freed, M. Liosatos, T. E. Morgan, I. Rozovsky, B. Trommer, K. L. Viola, P. Wals, C. Zhang, C. E. Finch, G. A. Krafft and W. L. Klein (1998) Diffusible, nonfibrillar ligands derived from A beta(1-42) are potent central nervous system neurotoxins. Proceedings of the National Academy of Sciences of the United States of America. 95, 6448-6453.
44 Selkoe, D. J. (1991) The Molecular Pathology of Alzheimers-Disease. Neuron. 6, 487-498.
45 Sommer, B. (2002) Alzheimer's disease and the amyloid cascade hypothesis: Ten years on. Current Opinion in Pharmacology. 2, 87-92.
46 Xing, Y. M. and K. Higuchi (2002) Amyloid fibril proteins. Mechanisms of Ageing and Development. 123, 1625-1636.
47 Shoghi-Jadid, K., J. R. Barrio, V. Kepe, H. M. Wu, G. W. Small, M. E. Phelps and S. C. Huang (2005) Imaging beta-amyloid fibrils in Alzheimer's disease: a critical analysis through simulation of amyloid fibril polymerization. Nucl Med Biol. 32, 337-351.
48 Buxbaum, J. D., K. N. Liu, Y. X. Luo, J. L. Slack, K. L. Stocking, J. J. Peschon, R. S. Johnson, B. J. Castner, D. P. Cerretti and R. A. Black (1998) Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor. Journal of Biological Chemistry. 273, 27765-27767.
49 Lammich, S., E. Kojro, R. Postina, S. Gilbert, R. Pfeiffer, M. Jasionowski, C. Haass and F. Fahrenholz (1999) Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease. Proceedings of the National Academy of Sciences of the United States of America. 96, 3922-3927.
50 Sinha, S., J. P. Anderson, R. Barbour, G. S. Basi, R. Caccavello, D. Davis, M. Doan, H. F. Dovey, N. Frigon, J. Hong, K. Jacobson-Croak, N. Jewett, P. Keim, J. Knops, I. Lieberburg, M. Power, H. Tan, G. Tatsuno, J. Tung, D. Schenk, P. Seubert, S. M. Suomensaari, S. W. Wang, D. Walker, J. Zhao, L. McConlogue and V. John (1999) Purification and cloning of amyloid precursor protein beta-secretase from human brain. Nature. 402, 537-540.
51 Vassar, R., B. D. Bennett, S. Babu-Khan, S. Kahn, E. A. Mendiaz, P. Denis, D. B. Teplow, S. Ross, P. Amarante, R. Loeloff, Y. Luo, S. Fisher, L. Fuller, S. Edenson, J. Lile, M. A. Jarosinski, A. L. Biere, E. Curran, T. Burgess, J. C. Louis, F. Collins, J. Treanor, G. Rogers and M. Citron (1999) beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science. 286, 735-741.
52 Yan, R. Q., M. J. Bienkowski, M. E. Shuck, H. Y. Miao, M. C. Tory, A. M. Pauley, J. R. Brashler, N. C. Stratman, W. R. Mathews, A. E. Buhl, D. B. Carter, A. G. Tomasselli, L. A. Parodi, R. L. Heinrikson and M. E. Gurney (1999) Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity. Nature. 402, 533-537.
53 De Strooper, B., P. Saftig, K. Craessaerts, H. Vanderstichele, G. Guhde, W. Annaert, K. Von Figura and F. Van Leuven (1998) Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature. 391, 387-390.
54 Lansbury, P. T., P. R. Costa, J. M. Griffiths, E. J. Simon, M. Auger, K. J. Halverson, D. A. Kocisko, Z. S. Hendsch, T. T. Ashburn, R. G. S. Spencer, B. Tidor and R. G. Griffin (1995) Structural Model for the Beta-Amyloid Fibril Based on Interstrand Alignment of an Antiparallel-Sheet Comprising a C-Terminal Peptide. Nature Structural Biology. 2, 990-998.
55 Benzinger, T. L. S., D. M. Gregory, T. S. Burkoth, H. Miller-Auer, D. G. Lynn, R. E. Botto and S. C. Meredith (1998) Propagating structure of Alzheimer's beta-amyloid((10-35)) is parallel beta-sheet with residues in exact register. Proceedings of the National Academy of Sciences of the United States of America. 95, 13407-13412.
56 Tycko, R., A. Petkova, N. Oyler, C. C. Chan and J. Balbach (2002) Probing the molecular structure of amyloid fibrils with solid state NMR. Biophysical Journal. 82, 187a-187a.
57 Der-Sarkissian, A., C. C. Jao, J. Chen and R. Langen (2003) Structural organization of alpha-synuclein fibrils studied by site-directed spin labeling. Journal of Biological Chemistry. 278, 37530-37535.
58 Torok, M., S. Milton, R. Kayed, P. Wu, T. McIntire, C. G. Glabe and R. Langen (2002) Structural and dynamic features of Alzheimer's A beta peptide in amyloid fibrils studied by site-directed spin labeling. Journal of Biological Chemistry. 277, 40810-40815.
59 Makin, O. S., E. Atkins, P. Sikorski, J. Johansson and L. C. Serpell (2005) Molecular basis for amyloid fibril formation and stability. Proceedings of the National Academy of Sciences of the United States of America. 102, 315-320.
60 Kelly, J. W. (2002) Towards an understanding of amyloidogenesis. Nature Structural Biology. 9, 323-325.
61 Mager, P. P., B. Penke, R. Walter, T. Harkany and W. Hartig (2002) Pathological peptide folding in Alzheimer's disease and other conformational disorders. Curr Med Chem. 9, 1763-1780.
62 Snow, C. D., N. Nguyen, V. S. Pande and M. Gruebele (2002) Absolute comparison of simulated and experimental protein-folding dynamics. Nature. 420, 102-106.
63 Zhou, R. H. (2003) Trp-cage: Folding free energy landscape in explicit water. Proceedings of the National Academy of Sciences of the United States of America. 100, 13280-13285.
64 Klimov, D. K., J. E. Straub and D. Thirumalai (2004) Aqueous urea solution destabilizes A beta(16-22) oligomers. Proceedings of the National Academy of Sciences of the United States of America. 101, 14760-14765.
65 Nguyen, H. D. and C. K. Hall (2004) Molecular dynamics simulations of spontaneous fibril formation by random-coil peptides. Proceedings of the National Academy of Sciences of the United States of America. 101, 16180-16185.
66 Xu, Y. C., J. J. Shen, X. M. Luo, W. L. Zhu, K. X. Chen, J. P. Ma and H. L. Jiang (2005) Conformational transition of amyloid beta-peptide. Proceedings of the National Academy of Sciences of the United States of America. 102, 5403-5407.
67 Barrow, C. J., A. Yasuda, P. T. M. Kenny and M. G. Zagorski (1992) Solution Conformations and Aggregational Properties of Synthetic Amyloid Beta-Peptides of Alzheimers-Disease - Analysis of Circular-Dichroism Spectra. Journal of Molecular Biology. 225, 1075-1093.
68 Coles, M., W. Bicknell, A. A. Watson, D. P. Fairlie and D. J. Craik (1998) Solution structure of amyloid beta-peptide(1-40) in a water-micelle environment. Is the membrane-spanning domain where we think it is? Biochemistry. 37, 11064-11077.
69 Shao, H. Y., S. C. Jao, K. Ma and M. G. Zagorski (1999) Solution structures of micelle-bound amyloid beta-(1-40) and beta-(1-42) peptides of Alzheimer's disease. Journal of Molecular Biology. 285, 755-773.
70 Soto, C., E. M. Castano, B. Frangione and N. C. Inestrosa (1995) The Alpha-Helical to Beta-Strand Transition in the Amino-Terminal Fragment of the Amyloid Beta-Peptide Modulates Amyloid Formation. Journal of Biological Chemistry. 270, 3063-3067.
71 Sticht, H., P. Bayer, D. Willbold, S. Dames, C. Hilbich, K. Beyreuther, R. W. Frank and P. Rosch (1995) Structure of Amyloid A4-(1-40)-Peptide of Alzheimers-Disease. European Journal of Biochemistry. 233, 293-298.
72 Barrow, C. J. and M. G. Zagorski (1991) Solution Structures of Beta Peptide and Its Constituent Fragments - Relation to Amyloid Deposition. Science. 253, 179-182.
73 Good, T. A. and R. M. Murphy (1995) Aggregation State-Dependent Binding of Beta-Amyloid Peptide to Protein and Lipid Components of Rat Cortical Homogenates. Biochemical and Biophysical Research Communications. 207, 209-215.
74 Serpell, L. C. (2000) Alzheimer's amyloid fibrils: structure and assembly. Bba-Mol Basis Dis. 1502, 16-30.
75 Nguyen, P. H., M. S. Li, G. Stock, J. E. Straub and D. Thirumalai (2007) Monomer adds to preformed structured oligomers of A beta-peptides by a two-stage dock-lock mechanism. Proceedings of the National Academy of Sciences of the United States of America. 104, 111-116.
76 Buck, M., S. Bouguet-Bonnet, R. W. Pastor and A. D. MacKerell (2006) Importance of the CMAP correction to the CHARMM22 protein force field: Dynamics of hen lysozyme. Biophysical Journal. 90, L36-L38.
77 Lazaridis, T. and M. Karplus (1999) Effective energy function for proteins in solution. Proteins-Structure Function and Genetics. 35, 133-152.
78 Schaefer, M. and M. Karplus (1996) A comprehensive analytical treatment of continuum electrostatics. Journal of Physical Chemistry. 100, 1578-1599.
79 Still, W. C., A. Tempczyk, R. C. Hawley and T. Hendrickson (1990) Semianalytical Treatment of Solvation for Molecular Mechanics and Dynamics. Journal of the American Chemical Society. 112, 6127-6129.
80 Feig, M., A. Onufriev, M. S. Lee, W. Im, D. A. Case and C. L. Brooks (2004) Performance comparison of generalized born and Poisson methods in the calculation of electrostatic solvation energies for protein structures. Journal of Computational Chemistry. 25, 265-284.
81 Sugita, Y. and Y. Okamoto (1999) Replica-exchange molecular dynamics method for protein folding. Chemical Physics Letters. 314, 141-151.
82 Dante, S., T. Hauss and N. A. Dencher (2002) beta-amyloid 25 to 35 is intercalated in anionic and zwitterionic lipid membranes to different extents. Biophysical Journal. 83, 2610-2616.
83 Esposito, C., A. Tedeschi, M. Scrima, G. D'Errico, M. F. Ottaviani, P. Rovero and A. M. D'Ursi (2006) Exploring interaction of beta-amyloid segment (25-35) with membrane models through paramagnetic probes. Journal of Peptide Science. 12, 766-774.

指導教授

陳文逸(Wen-Yih Chen)

審核日期

2008-7-22

推文