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論文中文名稱:利用分子模擬計算探討結合分子與類澱粉原纖維之嵌合模式及其在虛擬藥物篩選上的應用 [以論文名稱查詢館藏系統]
論文英文名稱:Molecular Modeling to Investigate the Binding Modes of Dye Molecules toward Amyloid Protofibril and Their Applications in Virtual Screening [以論文名稱查詢館藏系統]
院校名稱:臺北科技大學
學院名稱:工程學院
系所名稱:工程科技研究所
畢業學年度:98
出版年度:99
中文姓名:趙建華
英文姓名:Jian-Hua Zhao
研究生學號:94679024
學位類別:博士
語文別:英文
口試日期:2010-07-30
論文頁數:162
指導教授中文名:劉宣良
指導教授英文名:Hsuan-Liang Liu
口試委員中文名:林忻怡;黃志宏;陳文逸;劉公典;蔡偉博
口試委員英文名:Hsin-Yi Lin;Chih-Hung Huang;Wen-Yih Chen;Kung-Tien Liu;Wei-Bor Tsai
中文關鍵詞:類澱粉纖維正電子斷層造影阿茲海默症分子嵌合分子動力學模擬GNNQQNY胜肽乙型類澱粉蛋白
英文關鍵詞:amyloid fibrilspositron emission tomographyAlzheimer’s diseasemolecular dockingmolecular dynamics (MD) simulationsGNNQQNYAbeta
論文中文摘要:Thioflavin T與Congo red已被廣泛地用於定義組織內的類澱粉纖維超過半個世紀。它們的衍生物,如:[11C]PIB, [11C]SB-13, [18F]FDDNP, [11C]BF-227更被發展成正電子斷層造影的示蹤劑,並用以協助探查和顯現阿茲海默症中主要病徵的老年斑塊和神經纖維纏結。然而對於這些分子間結合的特定性、穩定性,以及它們在探測類澱粉纖維中所扮演的角色至今仍未釐清。為了更加暸解這些分子結合於類澱粉纖維的分子形式和結合位置的原貌,在本研究中,我們結合分子嵌合、評分函式、分子動力學模擬及分子力學-波以森波茲曼表面積法計算結合自由能,以探討:(i) Congo red與來自於酵母體普恩蛋白Sup35的類澱粉樣片段GNNQQNY原纖維的結合模式,及(ii) Thioflavin T及其中性衍生物BTA-1與乙型類澱粉蛋白原纖維的結合模式。本研究提供分子尺度下這些分子相互結合的原貌,而模擬結果更與過去實驗文獻一致。基於這些結果,我們進一步透過化學藥效基團和蛋白質結構為基礎的虛擬藥物篩選進行新藥搜尋,並且提出數個具有潛力的新型結合分子。這些結果預期將有助於日後設計新型聚集抑制劑或結合分子以達到臨床應用的目的。
論文英文摘要:Thioflavin T and Congo red have been commonly used to identify amyloid fibrils in tissues for more than half a century. Their derivatives have been developed as positron emission tomography (PET) tracers, such as [11C]PIB, [11C]SB-13, [18F]FDDNP, [11C]BF-227, and helped to detect and visualize amyloid plaques and neurofibrillary tangles, the hallmark pathologies accompanying the neurodegeneration involved in Alzheimer’s disease. However, the specificity and the stabilities of binding modes of these ligands and their roles in amyloid fibril detection remain elusive. To earn more insights into the nature of the molecular form in which the amyloid dye binds the fibril and the binding locations on the fibril, in this study, molecular docking, scoring functions, molecular dynamics (MD) simulations and binding free energy calculation using MM-PBSA (molecular mechanics Poisson-Boltzmann surface area) approaches were combined to investigate: (i) the binding modes of Congo red towards a protofibril formed by an amyloidogenic fragment (GNNQQNY) from the yeast prion protein Sup35 and (ii) the binding modes of Thioflavin T and its neutral analog BTA-1 to Abeta protofibrils. Our simulations provide molecular insights into the nature of the binding modes of amyloid dyes toward the amyloid protofibril, and these results are consistent with experimental data. Based on these results, we further performed pharmacophore- and structure-based virtual screening to search new binding molecules, and our results reveal several potential compounds. These results are useful to develop new aggregation inhibitors or molecular dyes for clinical purposes.
論文目次:ABSTRACT i
ACKNOWLEDGEMENT iv
CONTENTS v
TABLE CONTENTS x
FIGURE CONTENTS xi
Chapter 1 GENERAL INTRODUCTION 1
Chapter 2 LITERATURE REVIEW 3
2.1 Alzheimer’s disease 3
2.1.1 AD pathology 4
2.1.2 Amyloid cascade hypothesis 6
2.2 Amyloid fibril 8
2.2.1 Low-resolution structural studies of amyloid fibril 9
2.2.2 Recent advances on structural determination of amyloid fibril 10
2.2.2.1 Advances in X-ray crystallography for the determination of 3D structure of amyloid fibrils. 11
2.2.2.2 Steric zipper motif of GNNQQNY peptide 12
2.2.2.3 Recent advances in solid-state NMR for the determination of 3D structure of amyloid fibrils. 14
2.2.2.4 The 3D structure of Abeta amyloid fibril 15
2.3 The binding mode of molecular probe for amyloid fibril 19
2.3.1 Congo red (CR) 19
2.3.2 Binding mechanism of CR towards amyloid fibril 21
2.3.3 Congo red conformation and mechanism of the optical properties upon fibril binding 22
2.3.4 Molecular form of Congo Red bound to amyloid fibrils: monomer, dimer, or micelle? 23
2.3.5 Thioflavin T (ThT) 24
2.3.6 Binding mechanism and fluorescence enhancement of Thioflavin T to amyloid fibril 25
2.3.7 Orientation of Thioflavin T in its binding site 26
2.3.8 Thioflavin T conformation upon fibril binding 27
Chapter 3 MOLECULAR MODELING 29
3.1 Molecular docking 29
3.1.1 ZDOCK 31
3.1.1.1 Pairwise shape complementarity 31
3.1.1.2 Desolvation (DE) 32
3.1.1.3 Electrostatics (ELEC) 33
3.1.1.4 Search procedure 33
3.1.2 CDOCKER 34
3.2 Scoring function for docking 35
3.2.1 The types of Scoring functions 35
3.2.2 Scoring functions 37
3.2.2.1 Jain scoring function 38
3.2.2.2 LigScore1 scoring function 38
3.2.2.3 LigScore2 scoring function 39
3.2.2.4 Ludi scoring function 40
3.2.2.5 Piecewise Linear Potential (PLP) 41
3.2.2.6 PLP1 41
3.2.2.7 PLP2 43
3.2.2.8 Potential of Mean Force (PMF) 45
3.3 Molecular dynamics simulations 45
3.3.1 Force Fields 47
3.3.1.1 Overview Several Classical Force Fields 47
3.3.1.2 The Parameters in the Force Field 49
3.3.1.3 Functional Form of the CHARMm Force Field 55
3.3.2 Minimization 56
3.3.3 Equilibration 59
3.3.4 Molecular Dynamics 60
3.3.4.1 Constraints during Dynamics Simulations 62
3.3.4.2 Temperature Jump Techniques 64
3.4 Molecular Mechanics/Poisson–Boltzmann Surface Area Method 66
3.5 Pharmacophore modeling 68
Chapter 4 A Novel Integrated Approach to Identify the Binding Sites and Modes of Congo Red toward GNNQQNY Protofibril 70
4.1 Abstract 70
4.2 Introduction 71
4.3 Methods 73
4.3.1 Diverse and cluster ligand conformers 73
4.3.2 Global search of the CR binding sites on the GNNQQNY protofibril surface 75
4.3.3 Docking and consensus scoring 75
4.3.4 Molecular dynamics simulations and MM-PBSA binding free energy analysis 76
4.4 Results and discussion 77
4.4.1 The specificities and stabilities of CR binding modes 77
4.4.2 Comparing to the previous theoretical and experimental studies 82
4.5 Conclusions 85
4.6 Reference 86
Chapter 5 The Binding of Congo Red to GNNQQNY Protofibril and Structure-Based Virtual Screening for the Identification of New Aggregation Inhibitors 91
5.1 Abstract 91
5.2 Introduction 92
5.3 Methods 98
5.3.1 Identification of CR binding sites and modes for GNNQQNY protofibrils 98
5.3.1.1 Global search for the CR binding sites on the GNNQQNY protofibril surface 98
5.3.1.2 Docking and consensus scoring 99
5.3.1.3 Molecular dynamics simulations and MM-PBSA binding free energy analysis 99
5.3.2 Binding stability and affinity of CR analog towards the edge of GNNQQNY protofibrils 101
5.3.3 Virtual screening 101
5.4 Results and discussion 103
5.4.1 CR binding sites and modes for GNNQQNY protofibril oligomers 103
5.4.1.1 Four binding modes 103
5.4.1.2 MD simulations and MM-PBSA analysis 105
5.4.1.3 Discussion for complex A and D 107
5.4.1.4 Discussion for complex B 107
5.4.1.5 Discussion for complex C 108
5.4.2 Inhibition mechanism 109
5.4.2.1 Binding site D served as a potential inhibition site 109
5.4.2.2 The specific interactions involved in inhibition 110
5.4.3 The identification of new inhibitors by structure-based pharmacophore virtual screening 113
5.4.3.1 Structure-based pharmacophore generation 113
5.4.3.2 Virtual screening 115
5.4.3.3 Three potential inhibitors 117
5.5 Conclusions 119
5.6 Reference 121
Chapter 6 GENERAL CONCLUSIONS 128
Chapter 7 GENERAL REFERENCES 130
APPENDIX I The Binding of Thioflavin T and its neutral analog BTA-1 to Abeta Protofibrils and Structure-Based Virtual Screening for the Identification of New Molecular Probes 151
APPENDIX II MY PUBLICATION LIST 159
論文參考文獻:Ahn J. S., Lee J. H., Kim J. H. & Paik S. R. (2007) Novel method for quantitative determination of amyloid fibrils of [alpha]-synuclein and amyloid [beta]/A4 protein by using resveratrol. Anal. Biochem. 367, 259-265.
Andersen C. B., Yagi H., Manno M., Martorana V., Ban T., Christiansen G., Otzen D. E., Goto Y. & Rischel C. (2009) Branching in amyloid fibril growth. Biophys. J. 96, 1529-1536.
Astbury W. T., Dickinson S. & Bailey K. (1935) The X-ray interpretation of denaturation and the structure of the seed globulins. Biochem. J. 29, 2351-2360.
Balbach J. J., Ishii Y., Antzutkin O. N., Leapman R. D., Rizzo N. W., Dyda F., Reed J. & Tycko R. (2000) Amyloid Fibril Formation by A [beta] 16-22, a Seven-Residue Fragment of the Alzheimer's [beta]-Amyloid Peptide, and Structural Characterization by Solid State NMR†. Biochemistry (N. Y. ) 39, 13748-13759.
Ban T., Hamada D., Hasegawa K., Naiki H. & Goto Y. (2003) Direct observation of amyloid fibril growth monitored by thioflavin T fluorescence. J. Biol. Chem. 278, 16462-16465.
Baschnagel J., Binder K., Doruker P., Gusev A., Hahn O., Kremer K., Mattice W., Müller-Plathe F., Murat M. & Paul W. (2000) Bridging the gap between atomistic and coarse-grained models of polymers: status and perspectives. Adv. Polym. Sci. 152, 41-156.
Benditt E. P., Eriksen N. & Berglund C. (1970) Congo red dichroism with dispersed amyloid fibrils, an extrinsic cotton effect. Proc. Natl. Acad. Sci. U. S. A. 66, 1044-1051.
Benzinger T. L. S., Gregory D. M., Burkoth T. S., Miller-Auer H., Lynn D. G., Botto R. E. & Meredith S. C. (2000) Two-Dimensional Structure of [beta]-Amyloid (10− 35) Fibrils†. Biochemistry (N. Y. ) 39, 3491-3499.
Benzinger T. L. S., Gregory D. M., Burkoth T. S., Miller-Auer H., Lynn D. G., Botto R. E. & Meredith S. C. (1998) Propagating structure of Alzheimer’s [beta]-amyloid (10–35) is parallel β-sheet with residues in exact register. Proc. Natl. Acad. Sci. U. S. A. 95, 13407-13412.
Berg L., McKeel Jr D. W., Miller J. P., Storandt M., Rubin E. H., Morris J. C., Baty J., Coats M., Norton J. & Goate A. M. (1998) Clinicopathologic studies in cognitively healthy aging and Alzheimer disease: relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype. Arch. Neurol. 55, 326-335.
Biancalana M., Makabe K., Koide A. & Koide S. (2009) Molecular Mechanism of Thioflavin-T Binding to the Surface of [beta]-Rich Peptide Self-Assemblies. J. Mol. Biol. 385, 1052-1063.
Blennow K., de Leon M. J. & Zetterberg H. (2006) Alzheimer's disease. Lancet 368, 387-403.
Böhm H. J. (1998) Prediction of binding constants of protein ligands: a fast method for the prioritization of hits obtained from de novo design or 3D database search programs. J. Comput. Aided Mol. Des. 12, 309-309.
Böhm H. J. (1994) The development of a simple empirical scoring function to estimate the binding constant for a protein-ligand complex of known three-dimensional structure. J. Comput. Aided Mol. Des. 8, 243-256.
Braak H., Braak E. (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 82, 239-259.
Brion J. P. (1998) The role of neurofibrillary tangles in Alzheimer disease. Acta Neurol. Belg. 98, 165-174.
Brooks B. R., Bruccoleri R. E. & Olafson B. D. (1983) CHARMM: A program for macromolecular energy, minimization, and dynamics calculations. J. Comput. Chem. 4, 187-217.
Brooks B. R., Janezic D. & Karplus M. (1995) Harmonic analysis of large systems. I. Methodology. J. Comput. Chem. 16, 1522-1542.
Carter D. B., Chou K. C. (1998) A Model for Structure-Dependent Binding of Congo Red to Alzheimer [beta]-Amyloid Fibrils. Neurobiol. Aging 19, 37-40.
Caughey B., Ernst D. & Race R. E. (1993) Congo red inhibition of scrapie agent replication. J. Virol. 67, 6270.
Cavillon F., Elhaddaoui A., Alix A. J. P., Turrell S. & Dauchez M. (1997) Identification of the importance of the secondary structure of Alzheimer's disease amyloid. J. Mol. Struct. 408, 185-189.
Chander H., Chauhan A. & Chauhan V. (2007) Binding of Proteases to Fibrillar Amyloid-β Protein and its Inhibition by Congo Red. J. Alzheimer's Dis. 12, 261-269.
Chávez-Macıasd L., Menaa R. (2005) Regional conformational change involving phosphorylation of tau protein at the Thr 231, precedes the structural change detected by Alz-50 antibody in Alzheimer's disease. J. Alzheimer's Dis. 8, 29-41.
Chen R., Li L. & Weng Z. (2003) ZDOCK: an initial-stage protein-docking algorithm. Proteins 52, 80-87.
Chen R., Mintseris J., Janin J. & Weng Z. (2003) A protein-protein docking benchmark. Proteins 52, 88-91.
Chen R., Weng Z. (2003) A novel shape complementarity scoring function for protein-protein docking. Proteins 51, 397-408.
Chen R., Weng Z. (2002) Docking unbound proteins using shape complementarity, desolvation, and electrostatics. Proteins 47, 281-294.
Cohen T., Frydman-Marom A., Rechter M. & Gazit E. (2006) Inhibition of Amyloid Fibril Formation and Cytotoxicity by Hydroxyindole Derivatives. Biochemistry (N. Y. ) 45, 4727-4735.
Cooper J. H. (1974) Selective amyloid staining as a function of amyloid composition and structure. Histochemical analysis of the alkaline Congo red, standardized toluidine blue, and iodine methods. Lab. Invest. 31, 232-238.
Cummings J. L. (2004) Alzheimer's disease. N. Engl. J. Med. 351, 56-67+110.
Cummings J. L., Cole G. (2002) Alzheimer disease. J. Am. Med. Assoc. 287, 2335-2338.
Delacourte A., David J. P., Sergeant N., Buee L., Wattez A., Vermersch P., Ghozali F., Fallet-Bianco C., Pasquier F. & Lebert F. (1999) The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer's disease. Neurology 52, 1158-1165.
DeLellis R. A., Glenner G. G. & Ram J. (1968) Histochemical observations on amyloid with reference to polarization microscopy. J. Histochem. Cytochem. 16, 663-665.
Demaimay R., Harper J., Gordon H., Weaver D. & Caughey B. (1998) Structural aspects of Congo red as an inhibitor of protease-resistant prion protein formation. J. Neurochem. 71, 2534-2541.
Drachman D. A. (2006) Aging of the brain, entropy, and Alzheimer disease. Neurology 67, 1340-1352.
Dzwolak W., Pecul M. (2005) Chiral bias of amyloid fibrils revealed by the twisted conformation of Thioflavin T: an induced circular dichroism/DFT study. FEBS Lett. 579, 6601-6603.
Eriksen J. L., Janus C. G. (2007) Plaques, tangles, and memory loss in mouse models of neurodegeneration. Behav. Genet. 37, 79-100.
Ferri C. P., Prince M., Brayne C., Brodaty H., Fratiglioni L., Ganguli M., Hall K., Hasegawa K., Hendrie H. & Huang Y. (2006) Global prevalence of dementia: a Delphi consensus study. Lancet 366, 2112-2117.
Fodera V., Librizzi F., Groenning M., van de Weert M. & Leone M. (2008) Secondary nucleation and accessible surface in insulin amyloid fibril formation. J Phys Chem B 112, 3853-3858.
Foloppe N., Hubbard R. (2006) Towards predictive ligand design with free-energy based computational methods? Curr. Med. Chem. 13, 3583-3608.
Fradinger E.A., Maji S.K., Lazo N.D. & Teplow D.B. (2005) Studying amyloid beta-protein assembly in: Amyloid Precursor Protein (Xu, W.X.a.H., Ed.), pp. 83–110, CRC Press, Boca Ration, London, New York, Washington, DC
Gabb H. A., Jackson R. M. & Sternberg M. J. E. (1997) Modelling protein docking using shape complementarity, electrostatics and biochemical information1. J. Mol. Biol. 272, 106-120.
Gehlhaar D. K., Bouzida D. & Rejto P. A. (1999) Rational drug design: novel methodology and practical applications. ACS Symposium Series, 719; American Chemical Society: Washington, DC. 719, 292-311.
Gehlhaar D. K., Verkhivker G. M., Rejto P. A., Sherman C. J., Fogel D. R., Fogel L. J. & Freer S. T. (1995) Molecular recognition of the inhibitor AG-1343 by HIV-1 protease: conformationally flexible docking by evolutionary programming. Chem. Biol. 2, 317-324.
Giorgadze T. A., Shiina N., Baloch Z. W., Tomaszewski J. E. & Gupta P. K. (2004) Improved detection of amyloid in fat pad aspiration: An evaluation of Congo red stain by fluorescent microscopy. Diagn. Cytopathol. 31, 300-306.
Glenner G. G., Page D. L. & Eanes E. D. (1972) The relation of the properties of Congo red-stained amyloid fibrils to the beta-conformation. J. Histochem. Cytochem. 20, 821-826.
Goedert M., Crowther R. A. & Spillantini M. G. (1998) Tau mutations cause frontotemporal dementias. Neuron 21, 955-958.
Golde T. E. (2003) Alzheimer disease therapy: Can the amyloid cascade be halted? J. Clin. Invest. 111, 11-18.
Groenning M., Norrman M., Flink J. M., van de Weert M., Bukrinsky J. T., Schluckebier G. & Frokjaer S. (2007) Binding mode of Thioflavin T in insulin amyloid fibrils. J. Struct. Biol. 159, 483-497.
Groenning M., Olsen L., van de Weert M., Flink J. M., Frokjaer S. & Jørgensen F. S. (2007) Study on the binding of Thioflavin T to [beta]-sheet-rich and non-[beta]-sheet cavities. J. Struct. Biol. 158, 358-369.
Haass C., Selkoe D. J. (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide. Nat. Rev. Mol. Cell Biol. 8, 101-112.
Hardy J., Selkoe D. J. (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353-356.
Hardy J. A., Higgins G. A. (1992) Alzheimer's disease: The amyloid cascade hypothesis. Science 256, 184-185.
Harel M., Sonoda L. K., Silman I., Sussman J. L. & Rosenberry T. L. (2008) Crystal structure of thioflavin T bound to the peripheral site of Torpedo californica acetylcholinesterase reveals how thioflavin T acts as a sensitive fluorescent reporter of ligand binding to the acylation site. J. Am. Chem. Soc. 130, 7856-7861.
Harper J. D., Lansbury Jr P. T. (1997) Models of amyloid seeding in Alzheimer's disease and scrapie: mechanistic truths and physiological consequences of the time-dependent solubility of amyloid proteins. Annu. Rev. Biochem. 66, 385-407.
Harper J. D., Lieber C. M. & Lansbury Jr P. T. (1997) Atomic force microscopic imaging of seeded fibril formation and fibril branching by the Alzheimer's disease amyloid-[beta] protein. Chem. Biol. 4, 951-959.
Harper J. D., Wong S. S., Lieber C. M. & Lansbury P. T. (1997) Observation of metastable A [beta] amyloid protofibrils by atomic force microscopy. Chem. Biol. 4, 119-125.
Hodges J. R. (2006) Alzheimer's centennial legacy: origins, landmarks and the current status of knowledge concerning cognitive aspects. Brain 129, 2811-2822.
Homans S. W. (1990) A molecular mechanical force field for the conformational analysis of oligosaccharides: comparison of theoretical and crystal structures of Man. alpha. 1-3Man. beta. 1-4GlcNAc. Biochemistry (N. Y. ) 29, 9110-9118.
Hoshino M., Katou H., Hagihara Y., Hasegawa K., Naiki H. & Goto Y. (2002) Mapping the core of the β2-microglobulin amyloid fibril by H/D exchange. Nat. Struct. Biol. 9, 332-336.
Howie A. J., Brewer D. B. (2009) Optical properties of amyloid stained by Congo red: History and mechanisms. Micron 40, 285-301.
Hsia A. Y., Masliah E., McConlogue L., Yu G. Q., Tatsuno G., Hu K., Kholodenko D., Malenka R. C., Nicoll R. A. & Mucke L. (1999) Plaque-independent disruption of neural circuits in Alzheimer’s disease mouse models. Proc. Natl. Acad. Sci. U. S. A. 96, 3228-3233.
Inouye H., Fraser P. E. & Kirschner D. A. (1993) Structure of beta-crystallite assemblies formed by Alzheimer beta-amyloid protein analogues: analysis by x-ray diffraction. Biophys. J. 64, 502-519.
Jacobsen J. S., Reinhart P. & Pangalos M. N. (2005) Current concepts in therapeutic strategies targeting cognitive decline and disease modification in Alzheimer's disease. NeuroRx 2, 612-626.
Jain A. N. (1996) Scoring noncovalent protein-ligand interactions: a continuous differentiable function tuned to compute binding affinities. J. Comput. Aided Mol. Des. 10, 427-440.
Janezic D., Brooks B. R. (1995) Harmonic analysis of large systems. II. Comparison of different protein models. J. Comput. Chem. 16, 1543-1553.
Janezic D., Venable R. M. & Brooks B. R. (1995) Harmonic analysis of large systems. III. Comparison with molecular dynamics. J. Comput. Chem. 16, 1554-1566.
Jarrett J. T., Berger E. P. & Lansbury Jr P. T. (1993) The carboxy terminus of the. beta. amyloid protein is critical for the seeding of amyloid formation: Implications for the pathogenesis of Alzheimer's disease. Biochemistry (N. Y. ) 32, 4693-4697.
Jin L. W., Claborn K. A., Kurimoto M., Geday M. A., Maezawa I., Sohraby F., Estrada M., Kaminksy W. & Kahr B. (2003) Imaging linear birefringence and dichroism in cerebral amyloid pathologies. Proc. Natl. Acad. Sci. U. S. A. 100, 15294-15298.
Joseph-McCarthy D., Baber J. C., Feyfant E., Thompson D. C. & Humblet C. (2007) Lead optimization via high-throughput molecular docking. Curr. Opin. Drug Discov. Devel. 10, 264-274.
Kang J., Lemaire H. G., Unterbeck A., Salbaum J. M., Masters C. L., Grzeschik K. H., Multhaup G., Beyreuther K. & Müller-Hill B. (1987) The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325, 733-736.
Kardos J., Okuno D., Kawai T., Hagihara Y., Yumoto N., Kitagawa T., Závodszky P., Naiki H. & Goto Y. (2005) Structural studies reveal that the diverse morphology of [beta] 2-microglobulin aggregates is a reflection of different molecular architectures. Biochim. Biophys. Acta 1753, 108-120.
Kheterpal I., Cook K. D. & Wetzel R. (2006) Hydrogen/deuterium exchange mass spectrometry analysis of protein aggregates. Meth. Enzymol. 413, 140-166.
Khurana R., Coleman C., Ionescu-Zanetti C., Carter S. A., Krishna V., Grover R. K., Roy R. & Singh S. (2005) Mechanism of thioflavin T binding to amyloid fibrils. J. Struct. Biol. 151, 229-238.
Khurana R., Uversky V. N., Nielsen L. & Fink A. L. (2001) Is Congo red an amyloid-specific dye? J. Biol. Chem. 276, 22715-22721.
Kim Y. S., Randolph T. W., Manning M. C., Stevens F. J. & Carpenter J. F. (2003) Congo red populates partially unfolded states of an amyloidogenic protein to enhance aggregation and amyloid fibril formation. J. Biol. Chem. 278, 10842-10850.
Kitchen D. B., Decornez H., Furr J. R. & Bajorath J. (2004) Docking and scoring in virtual screening for drug discovery: methods and applications. Nat. Rev. Drug. Discov. 3, 935-949.
Klunk W. E., Debnath M. L. & Pettegrew J. W. (1995) Chrysamine-G binding to Alzheimer and control brain: autopsy study of a new amyloid probe. Neurobiol. Aging 16, 541-548.
Klunk W. E., Debnath M. L. & Pettegrew J. W. (1994) Development of small molecule probes for the beta-amyloid protein of Alzheimer's disease. Neurobiol. Aging 15, 691-698.
Klunk W. E., Jacob R. F. & Mason R. P. (1999) Quantifying Amyloid [beta]-Peptide (A [beta]) Aggregation Using the Congo Red-A [beta](CR-A [beta]) Spectrophotometric Assay. Anal. Biochem. 266, 66-76.
Klunk W. E., Pettegrew J. W. & Abraham D. J. (1989) Two simple methods for quantifying low-affinity dye-substrate binding. J. Histochem. Cytochem. 37, 1293-1297.
Klunk W. E., Pettegrew J. W. & Abraham D. J. (1989) Quantitative evaluation of congo red binding to amyloid-like proteins with a beta-pleated sheet conformation. J. Histochem. Cytochem. 37, 1273-1281.
Kollman P. A., Massova I., Reyes C., Kuhn B., Huo S., Chong L., Lee M., Lee T., Duan Y. & Wang W. (2000) Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc. Chem. Res. 33, 889-897.
Krammer A., Kirchhoff P. D., Jiang X., Venkatachalam C. M. & Waldman M. (2005) LigScore: a novel scoring function for predicting binding affinities. J. Mol. Graph. Model. 23, 395-407.
Krebs M. R. H., Bromley E. H. C. & Donald A. M. (2005) The binding of thioflavin-T to amyloid fibrils: localisation and implications. J. Struct. Biol. 149, 30-37.
Lambert M. P., Barlow A. K., Chromy B. A., Edwards C., Freed R., Liosatos M., Morgan T. E., Rozovsky I., Trommer B. & Viola K. L. (1998) Diffusible, nonfibrillar ligands derived from Aβ1–42 are potent central nervous system neurotoxins. Proc. Natl. Acad. Sci. U. S. A. 95, 6448-6453.
Lansbury P. T., Costa P. R., Griffiths J. M., Simon E. J., Auger M., Halverson K. J., Kocisko D. A., Hendsch Z. S., Ashburn T. T. & Spencer R. G. S. (1995) Structural model for the β-amyloid fibril based on interstrand alignment of an antiparallel-sheet comprising a C-terminal peptide. Nat. Struct. Biol. 2, 990-998.
Lengauer T., Rarey M. (1996) Computational methods for biomolecular docking. Curr. Opin. Struct. Biol. 6, 402-406.
Lensink M. F., Méndez R. & Wodak S. J. (2007) Docking and scoring protein complexes: CAPRI 3rd Edition. Proteins 69, 704-718.
LeVine III H. (1995) Thioflavin T interaction with amyloid beta-sheet structures. Amyloid Int. J. Exp. Clin. Invest. 2, 1-6.
LeVine III H., Thioflavine T. (1993) Thioflavine T interaction with synthetic Alzheimer's disease beta-amyloid peptides: detection of amyloid aggregation in solution. Protein Sci. 2, 404-410.
LeVine III H. (1999) Quantification of beta-sheet amyloid fibril structures with thioflavin T. Meth. Enzymol. 309, 274-284.
Levine III H. (1997) Stopped-Flow Kinetics Reveal Multiple Phases of Thioflavin T Binding to Alzheimer [beta](1-40) Amyloid Fibrils. Arch. Biochem. Biophys. 342, 306-316.
Li L., Darden T. A., Bartolotti L., Kominos D. & Pedersen L. G. (1999) An atomic model for the pleated [beta]-sheet structure of A [beta] amyloid protofilaments. Biophys. J. 76, 2871-2878.
Lindgren M., Sörgjerd K. & Hammarström P. (2005) Detection and characterization of aggregates, prefibrillar amyloidogenic oligomers, and protofibrils using fluorescence spectroscopy. Biophys. J. 88, 4200-4212.
Liwo A., Khalili M. & Scheraga H. A. (2005) Ab initio simulations of protein-folding pathways by molecular dynamics with the united-residue model of polypeptide chains. Proc. Natl. Acad. Sci. U. S. A. 102, 2362.
Liwo A., Wawak R. J., Scheraga H. A., Pincus M. R. & Rackovsky S. (1993) Prediction of protein conformation on the basis of a search for compact structures: test on avian pancreatic polypeptide. Protein Sci. 2, 1715-1731.
Loksztejn A., Dzwolak W. (2008) Chiral bifurcation in aggregating insulin: an induced circular dichroism study. J. Mol. Biol. 379, 9-16.
Lorenzo A., Yankner B. A. (1994) Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red. Proc. Natl. Acad. Sci. U. S. A. 91, 12243-12247.
Lovestone S., McLoughlin D. M. (2002) Protein aggregates and dementia: is there a common toxicity? J. Neurol. Neurosurg. Psychiatry 72, 152-161.
Lührs T., Ritter C., Adrian M., Riek-Loher D., Bohrmann B., Döbeli H., Schubert D. & Riek R. (2005) 3D structure of Alzheimer's amyloid-β (1–42) fibrils. Proc. Natl. Acad. Sci. U. S. A. 102, 17342-17347.
Makin O. S., Serpell L. C. (2005) Structures for amyloid fibrils. FEBS J 272, 5950-5961.
Mann D. M., Iwatsubo T., Ihara Y., Cairns N. J., Lantos P. L., Bogdanovic N., Lannfelt L., Winblad B., Maat-Schieman M. L. & Rossor M. N. (1996) Predominant deposition of amyloid-beta 42 (43) in plaques in cases of Alzheimer's disease and hereditary cerebral hemorrhage associated with mutations in the amyloid precursor protein gene. Am. J. Pathol. 148, 1257-1266.
Margittai M., Langen R. (2008) Fibrils with parallel in-register structure constitute a major class of amyloid fibrils: molecular insights from electron paramagnetic resonance spectroscopy. Q. Rev. Biophys. 41, 265-297.
Marrink S. J., de Vries A. H. & Mark A. E. (2004) Coarse grained model for semiquantitative lipid simulations. J. Phys. Chem. B 108, 750-760.
Marrink S. J., Risselada J. & Mark A. E. (2005) Simulation of gel phase formation and melting in lipid bilayers using a coarse grained model. Chem. Phys. Lipids 135, 223-244.
Mason J. M., Kokkoni N., Stott K. & Doig A. J. (2003) Design strategies for anti-amyloid agents. Curr. Opin. Struct. Biol. 13, 526-532.
Massova I., Kollman P. A. (2000) Combined molecular mechanical and continuum solvent approach (MM-PBSA/GBSA) to predict ligand binding. Perspect. Drug Discov. Des. 18, 113-135.
Masters C. L., Cappai R., Barnham K. J. & Villemagne V. L. (2006) Molecular mechanisms for Alzheimer's disease: implications for neuroimaging and therapeutics. J. Neurochem. 97, 1700-1725.
Masuda Y., Irie K., Murakami K., Ohigashi H., Ohashi R., Takegoshi K., Shimizu T. & Shirasawa T. (2005) Verification of the turn at positions 22 and 23 of the [beta]-amyloid fibrils with Italian mutation using solid-state NMR. Bioorg. Med. Chem. 13, 6803-6809.
Mauro M., Craparo E. F., Podestą A., Bulone D., Carrotta R., Martorana V., Tiana G. & San Biagio P. L. (2007) Kinetics of different processes in human insulin amyloid formation. J. Mol. Biol. 366, 258-274.
Mayo S. L., Olafson B. D. & Goddard W. A. (1990) DREIDING: a generic force field for molecular simulations. J. Phys. Chem. 94, 8897-8909.
McParland V. J., Kad N. M., Kalverda A. P., Brown A., Kirwin-Jones P., Hunter M. G., Sunde M. & Radford S. E. (2000) Partially Unfolded States of [beta] 2-Microglobulin and Amyloid Formation in Vitro†. Biochemistry (N. Y. ) 39, 8735-8746.
Mishra R., Sellin D., Radovan D., Gohlke A. & Winter R. (2009) Inhibiting islet amyloid polypeptide fibril formation by the red wine compound resveratrol. Chem. Bio. Chem. 10, 445-449.
Miura T., Yamamiya C., Sasaki M., Suzuki K. & Takeuchi H. (2002) Binding mode of Congo Red to Alzheimer's amyloid β-peptide studied by UV Raman spectroscopy. J. Raman Spectrosc. 33, 530-535.
Momany F. A., Rone R. (1992) Validation of the general purpose QUANTA® 3.2/CHARMm® force field. J. Comput. Chem. 13, 888-900.
Morris J. C., Kimberly A., Quaid K., Holtzman D. M., Kantarci K., Kaye J., Reiman E. M., Klunk W. E. & Siemers E. R. (2005) Role of biomarkers in studies of presymptomatic Alzheimer's disease. Alzheimers Dement. 1, 145-151.
Mott R. T., Hulette C. M. (2005) Neuropathology of Alzheimer's disease. Neuroimaging Clin. N. Am. 15, 755-765.
Mourtzis N., Cordoyiannis G., Nounesis G. & Yannakopoulou K. (2003) Single and Double Threading of Congo Red into γ-Cyclodextrin. Solution Structures and Thermodynamic Parameters of 1: 1 and 2: 2 Adducts, as Obtained from NMR Spectroscopy and Microcalorimetry. Supramol. Chem. 15, 639-649.
Mucke L., Masliah E., Yu G. Q., Mallory M., Rockenstein E. M., Tatsuno G., Hu K., Kholodenko D., Johnson-Wood K. & McConlogue L. (2000) High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J. Neurosci. 20, 4050-4058.
Muegge I. (2006) PMF scoring revisited. J. Med. Chem. 49, 5895-5902.
Muegge I., Martin Y. C. (1999) A general and fast scoring function for protein− ligand interactions: A simplified potential approach. J. Med. Chem. 42, 791-804.
Müller M., Katsov K. & Schick M. (2003) Coarse-grained models and collective phenomena in membranes: computer simulation of membrane fusion. J. Polym. Sci. B Polym. Phys. 41, 1441-1450.
Naiki H., Higuchi K., Hosokawa M. & Takeda T. (1989) Fluorometric determination of amyloid fibrils in vitro using the fluorescent dye, thioflavine T* 1. Anal. Biochem. 177, 244-249.
Naiki H., Higuchi K., Nakakuki K. & Takeda T. (1991) Kinetic analysis of amyloid fibril polymerization in vitro. Lab. Invest. 65, 104-110.
Nelson R., Eisenberg D. (2006) Recent atomic models of amyloid fibril structure. Curr. Opin. Struct. Biol. 16, 260-265.
Nelson R., Sawaya M. R., Balbirnie M., Madsen A. Ø., Riekel C., Grothe R. & Eisenberg D. (2005) Structure of the cross-β spine of amyloid-like fibrils. Nature 435, 773-778.
Nielsen L., Khurana R., Coats A., Frokjaer S., Brange J., Vyas S., Uversky V. N. & Fink A. L. (2001) Effect of Environmental Factors on the Kinetics of Insulin Fibril Formation: Elucidation of the Molecular Mechanism†. Biochemistry (N. Y. ) 40, 6036-6046.
Parihar M. S., Hemnani T. (2004) Alzheimer's disease pathogenesis and therapeutic interventions. J. Clin. Neurosci. 11, 456-467.
Pettersson T, Konttinen YT (2009) Semin Arthritis Rheum (in press)
Pedersen J. S., Dikov D., Flink J. L., Hjuler H. A., Christiansen G. & Otzen D. E. (2006) The changing face of glucagon fibrillation: Structural polymorphism and conformational imprinting. J. Mol. Biol. 355, 501-523.
Pepys M. B. (2001) Pathogenesis, diagnosis and treatment of systemic amyloidosis. Philos. Trans. R. Soc. London, Ser. B 356, 203-211.
Petkova A. T., Ishii Y., Balbach J. J., Antzutkin O. N., Leapman R. D., Delaglio F. & Tycko R. (2002) A structural model for Alzheimer's β-amyloid fibrils based on experimental constraints from solid state NMR. Proc. Natl. Acad. Sci. U. S. A. 99, 16742-16747.
Porat Y., Abramowitz A. & Gazit E. (2006) Inhibition of amyloid fibril formation by polyphenols: structural similarity and aromatic interactions as a common inhibition mechanism. Chem. Biol. Drug Des. 67, 27-37.
Praticņ D., Delanty N. (2000) Oxidative injury in diseases of the central nervous system: focus on Alzheimer's disease. Am. J. Med. 109, 577-585.
Prokuda O. V., Belosludov V. R., Igumenov I. K. & Stabnikov P. A. (2006) The calculation of van-der-waals interaction energy in the crystales of metal β-diketonates (metal= Al, Cr, Fe and Ir). J. Phys. : Conf. Ser. 29, 8-13.
Rajamani R., Good A. C. (2007) Ranking poses in structure-based lead discovery and optimization: current trends in scoring function development. Curr. Opin. Drug Discov. Devel. 10, 308-315.
Rice D. P., Fillit H. M., Max W., Knopman D. S., Lloyd J. R. & Duttagupta S. (2001) Prevalence, costs, and treatment of Alzheimer's disease and related dementia: a managed care perspective. Am. J. Manag. Care 7, 809-820.
Ritter C., Maddelein M. L., Siemer A. B., Lührs T., Ernst M., Meier B. H., Saupe S. J. & Riek R. (2005) Correlation of structural elements and infectivity of the HET-s prion. Nature 435, 844-848.
Robertson T. A., Varani G. (2007) An all-atom, distance-dependent scoring function for the prediction of protein-DNA interactions from structure. Proteins 66, 359-374.
Romhányi G. (1971) Selective differentiation between amyloid and connective tissue structures based on the collagen specific topo-optical staining reaction with Congo red. Virchows Arch. A: Pathol. Anat. 354, 209-222.
Ross C. A., Poirier M. A. (2004) Protein aggregation and neurodegenerative disease. Brain Res. Rev. 53, 135-160.
Roterman I., KrUl M., Nowak M., Konieczny L., Rybarska J., Stopa B., Piekarska B. & Zemanek G. (2001) Why Congo red binding is specific for amyloid proteins - model studies and a computer analysis approach. Med. Sci. Monit. 7, 771-784.
Sabaté R., Lascu I. & Saupe S. J. (2008) On the binding of Thioflavin-T to HET-s amyloid fibrils assembled at pH 2. J. Struct. Biol. 162, 387-396.
Sabaté R., Saupe S. J. (2007) Thioflavin T fluorescence anisotropy: an alternative technique for the study of amyloid aggregation. Biochem. Biophys. Res. Commun. 360, 135-138.
Saeed S. M., Fine G. (1967) Thioflavin-T for amyloid detection. Am. J. Clin. Pathol. 47, 588-593.
Saido T. C., Iwata N. (2006) Metabolism of amyloid [beta] peptide and pathogenesis of Alzheimer's disease:: Towards presymptomatic diagnosis, prevention and therapy. Neurosci. Res. 54, 235-253.
Salemme F. R. (1983) Structural properties of protein beta-sheets. Prog. Biophys. Mol. Biol. 42, 95-133.
Sastre M., Klockgether T. & Heneka M. T. (2006) Contribution of inflammatory processes to Alzheimer's disease: molecular mechanisms. Int. J. Dev. Neurosci. 24, 167-176.
Sawaya M. R., Sambashivan S., Nelson R., Ivanova M. I., Sievers S. A., Apostol M. I., Thompson M. J., Balbirnie M., Wiltzius J. J. W. & McFarlane H. T. (2007) Atomic structures of amyloid cross-beta spines reveal varied steric zippers. Nature 447, 453-457.
Şen S., Başdemir G. (2003) Diagnosis of renal amyloidosis using Congo red fluorescence. Pathol. Int. 53, 534-538.
Sereikaite½ J., Bumelis V. A. (2006) Congo red interaction with α-proteins. Acta. Biochim. Pol. 53, 87-92.
Shelley J. C., Shelley M. Y. (2000) Computer simulation of surfactant solutions. Curr. Opin. Colloid. Interface Sci. 5, 101-110.
Sipe J. D., Cohen A. S. (2000) Review: History of the Amyloid Fibril. J. Struct. Biol. 130, 88-98.
Skowronek M., Stopa B., Konieczny L., Rybarska J., Piekarska B., Szneler E., Bakalarski G. & Roterman I. (1998) Self-assembly of Congo red-a theoretical and experimental approach to identify its supramolecular organization in water and salt solutions. Biopolymers 46, 267-281.
Sorrentino G., Bonavita V. (2007) Neurodegeneration and Alzheimer’s disease: the lesson from tauopathies. Neurol. Sci. 28, 63-71.
Spillantini M. G., Goedert M. (1998) Tau protein pathology in neurodegenerative diseases. Trends Neurosci. 21, 428-433.
Srinivasan J., Cheatham III T. E., Cieplak P., Kollman P. A. & Case D. A. (1998) Continuum solvent studies of the stability of DNA, RNA, and phosphoramidate− DNA helices. J. Am. Chem. Soc. 120, 9401-9409.
Stopa B., Górny M., Konieczny L., Piekarska B., Rybarska J., Skowronek M. & Roterman I. (1998) Supramolecular ligands: monomer structure and protein ligation capability. Biochimie 80, 963-968.
Stopa B., Piekarska B., Konieczny L., Rybarska J., Spólnik P., Zemanek G., Roterman I. & Król M. (2003) The structure and protein binding of amyloid-specific dye reagents. Acta. Biochim. Pol. 50, 1213-1228.
Stromer T., Serpell L. C. (2005) Structure and morphology of the Alzheimer's amyloid fibril. Microsc. Res. Tech. 67, 210-217.
Stsiapura V. I., Maskevich A. A., Kuzmitsky V. A., Turoverov K. K. & Kuznetsova I. M. (2007) Computational study of thioflavin T torsional relaxation in the excited state. J Phys Chem A 111, 4829-4835.
Sunde M., Blake C. (1997) The structure of amyloid fibrils by electron microscopy and X-ray diffraction. Adv. Protein Chem. 50, 123-124.
Sunde M., Serpell L. C., Bartlam M., Fraser P. E., Pepys M. B. & Blake C. C. F. (1997) Common core structure of amyloid fibrils by synchrotron X-ray diffraction. J. Mol. Biol. 273, 729-739.
Tanzi R. E., Bertram L. (2001) New frontiers in Alzheimer's disease genetics. Neuron 32, 181-184.
Toyama B. H., Kelly M. J. S., Gross J. D. & Weissman J. S. (2007) The structural basis of yeast prion strain variants. Nature 449, 233-237.
Turnell W. G., Finch J. T. (1992) Binding of the dye congo red to the amyloid protein pig insulin reveals a novel homology amongst amyloid-forming peptide sequences. J. Mol. Biol. 227, 1205-1223.
Vassar P. S., Culling C. F. (1959) Fluorescent stains, with special reference to amyloid and connective tissues. Arch. Pathol. 68, 487-498.
Verdile G., Fuller S., Atwood C. S., Laws S. M., Gandy S. E. & Martins R. N. (2004) The role of beta amyloid in Alzheimer's disease: still a cause of everything or the only one who got caught? Pharmacol. Res. 50, 397-409.
Vilar M., Chou H. T., Lührs T., Maji S. K., Riek-Loher D., Verel R., Manning G., Stahlberg H. & Riek R. (2008) The fold of alpha-synuclein fibrils. Proc. Natl. Acad. Sci. U. S. A. 105, 8637-8642.
Virchow R (1854) Virchows Arch Pathol Anat Physiol Klin Med 6:416–426
von Strauss E., Viitanen M., De Ronchi D., Winblad B. & Fratiglioni L. (1999) Aging and the occurrence of dementia: findings from a population-based cohort with a large sample of nonagenarians. Arch. Neurol. 56, 587-592.
Voropai E. S., Samtsov M. P., Kaplevskii K. N., Maskevich A. A., Stepuro V. I., Povarova O. I., Kuznetsova I. M., Turoverov K. K., Fink A. L. & Uverskii V. N. (2003) Spectral properties of thioflavin T and its complexes with amyloid fibrils. J. Appl. Spectrosc. 70, 868-874.
Wall J., Murphy C. L. & Solomon A. (1999) In vitro immunoglobulin light chain fibrillogenesis. Methods Enzymol. 309, 204-217.
Walsh D. M., Lomakin A., Benedek G. B., Condron M. M. & Teplow D. B. (1997) Amyloid β-protein fibrillogenesis: Detection of a protofibrillar intermediate. J. Biol. Chem. 272, 22364-22372.
Westerman M. A., Cooper-Blacketer D., Mariash A., Kotilinek L., Kawarabayashi T., Younkin L. H., Carlson G. A., Younkin S. G. & Ashe K. H. (2002) The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer's disease. J. Neurosci. 22, 1858-1867.
Westermark G. T., Johnson K. H. & Westermark P. (1999) Staining methods for identification of amyloid in tissue. Meth. Enzymol. 309, 3-25.
Westermark P., Benson M. D., Buxbaum J. N., Cohen A. S., Frangione B., Ikeda S. I., Masters C. L., Merlini G., Saraiva M. J. & Sipe J. D. (2007) A primer of amyloid nomenclature. Amyloid 14, 179-183.
Wolber G., Seidel T., Bendix F. & Langer T. (2008) Molecule-pharmacophore superpositioning and pattern matching in computational drug design. Drug Discov. Today 13, 23-29.
Wong C. W., Quaranta V. & Glenner G. G. (1985) Neuritic plaques and cerebrovascular amyloid in Alzheimer disease are antigenically related. Proc. Natl. Acad. Sci. U.
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