The role of molecular simulations in the development of inhibitors of amyloid β-peptide aggregation for the treatment of Alzheimers disease

ACS Chemical Neuroscience

Volumn 3, Issue 11, 2012, Pages 845-856

  Lemkul, Justin A ^a   Bevan, David R ^a  

^a VIRGINIA POLYTECHNIC INSTITUTE AND STATE UNIVERSITY   (United States)

Author keywords

amyloid; docking; Modeling; molecular dynamics; therapeutics

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; CONGO RED; IBUPROFEN; NAPROXEN;

ALZHEIMER DISEASE; CAUSE OF DEATH; DISEASE COURSE; DRUG DESIGN; HUMAN; INCIDENCE; MOLECULAR DOCKING; MOLECULAR DYNAMICS; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; PROTEIN AGGREGATION; REVIEW; SENILE DEMENTIA; THEORETICAL MODEL; UNITED STATES;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; COMPUTER SIMULATION; DRUG DISCOVERY; HUMANS; MOLECULAR DOCKING SIMULATION; MOLECULAR DYNAMICS SIMULATION;

EID: 84869798713     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/cn300091a     Document Type: Review

References (139)

1. 2011, Alzheimers Disease Facts and Figures, http://www.alz.org/downloads/ Facts-Figures-2011.pdf.
2. Hardy, J. A. and Higgins, G. A. (1992) Alzheimers Disease: The Amyloid Cascade Hypothesis Science 256, 184-185
3. Kayed, R., Head, E., Thompson, J. L., McIntire, T. M., Milton, S. C., Cotman, C. W., and Glabe, C. G. (2003) Common Structure of Soluble Amyloid Oligomers Implies Common Mechanism of Pathogenesis Science 300, 486-489
4. Kayed, R., Sokolov, Y., Edmonds, B., McIntire, T. M., Milton, S. C., Hall, J. E., and Glabe, C. G. (2004) Permeabilization of Lipid Bilayers Is a Common Conformation-dependent Activity of Soluble Amyloid Oligomers in Protein Misfolding Diseases J. Biol. Chem. 279, 46363-46366
5. Tayeb, H. O., Yang, H. D., Price, B. H., and Tarazi, F. I. (2012) Pharmacotherapies for Alzheimers disease: Beyond cholinesterase inhibitors Pharmacol. Ther. 134, 8-25
6. Yamin, G., Ono, K., Inayathullah, M., and Teplow, D. B. (2008) Amyloid β-Protein Assembly as a Therapeutic Target of Alzheimers Disease Curr. Pharm. Des. 14, 3231-3246
7. Ghanta, J., Shen, C.-L., Kiessling, L. L., and Murphy, R. M. (1996) A Strategy for Designing Inhibitors of β-Amyloid Toxicity J. Biol. Chem. 271, 29525-29528
8. Tjernberg, L. O., Naslund, J., Lindqvist, F., Johansson, J., Karlstrom, A. R., Thyberg, J., Terenius, L., and Nordstedt, C. (1996) Arrest of β-Amyloid Fibril Formation by a Pentapeptide Ligand J. Biol. Chem. 271, 8545-8548
9. Lowe, T. L., Strzelec, A., Kiessling, L. L., and Murphy, R. M. (2001) Structure-Function Relationships for Inhibitors of β-Amyloid Toxicity Containing the Recognition Sequence KLVFF Biochemistry 40, 7882-7889
10. Gibson, T. J. and Murphy, R. M. (2005) Design of Peptidyl Compounds That Affect β-Amyloid Aggregation: Importance of Surface Tension and Context Biochemistry 44, 8898-8907
11. Gestewicki, J. E., Crabtree, G. R., and Graef, I. A. (2004) Harnessing Chaperones to Generate Small-Molecule Inhibitors of Amyloid β Aggregation Science 306, 865-869
12. Ono, K., Yoshiike, Y., Takashima, A., Hasegawa, K., Naiki, H., and Yamada, M. (2004) Vitamin A exhibits potent antiamyloidogenic and fibril-destabilizing effects in vitro Exp. Neurol. 189, 380-392
13. Ono, K., Hasegawa, K., Yamada, M., and Naiki, H. (2002) Nicotine Breaks Down Preformed Alzheimers β-Amyloid Fibrils in Vitro Biol. Psychiatry 52, 880-886
14. Ono, K., Hasegawa, K., Naiki, H., and Yamada, M. (2004) Anti-amyloidogenic activity of tannic acid and its activity to destabilize Alzheimers β-amyloid fibrils in vitro Biochim. Biophys. Acta 1690, 193-202
15. Ono, K., Hasegawa, K., Yoshiike, Y., Takashima, A., Yamada, M., and Naiki, H. (2002) Nordihydroguaiaretic acid potently breaks down pre-formed Alzheimers β-amyloid fibrils in vitro J. Neurochem. 81, 434-440
16. Ono, K., Hasegawa, K., Naiki, H., and Yamada, M. (2004) Curcumin Has Potent Anti-Amyloidogenic Effects for Alzheimers β-Amyloid Fibrils In Vitro J. Neurosci. Res. 75, 742-750
17. Ono, K., Yoshiike, Y., Takashima, A., Hasegawa, K., Naiki, H., and Yamada, M. (2003) Potent anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro: implications for the prevention and therapeutics of Alzheimers disease J. Neurochem. 87, 172-181
18. Ono, K., Li, L., Takamura, Y., Yoshiike, Y., Zhu, L., Han, F., Mao, X., Ikeda, T., Takasaki, J.-i., Nishijo, H., Takashima, A., Teplow, D. B., Zagorski, M. G., and Yamada, M. (2012) Phenolic Compounds Prevent Amyloid β-Protein Oligomerization and Synaptic Dysfunction by Site-specific Binding J. Biol. Chem. 287, 14631-14643
19. Sinha, S., Du, Z., Maiti, P., Klarner, F.-G., Schrader, T., Wang, C., and Bitan, G. (2012) Comparison of Three Amyloid Assembly Inhibitors: The Sugar scyllo- Inositol, the Polyphenol Epigallocatechin Gallate, and the Molecular Tweezer CLR01 ACS Chem. Neurosci. 3, 451-458
20. Sinha, S., Lopes, D. H., Du, Z., Pang, E. S., Shanmugam, A., Lomakin, A., Talbiersky, P., Tennstaedt, A., McDaniel, K., Bakshi, R., Kuo, P. Y., Ehrmann, M., Benedek, G. B., Loo, J. A., Klarner, F. G., Schrader, T., Wang, C., and Bitan, G. (2011) Lysine-specific molecular tweezers are broad-spectrum inhibitors of assembly and toxicity of amyloid proteins J. Am. Chem. Soc. 133, 16958-16969
21. Teplow, D. B., Lazio, N. D., Bitan, G., Bernstein, S., Wyttenbach, T., Bowers, M. T., Baumketner, A., Shea, J.-E., Urbanc, B., Cruz, L., Borreguero, J., and Stanley, H. E. (2006) Elucidating Amyloid β-Protein Folding and Assembly: A Multidisciplinary Approach Acc. Chem. Res. 39, 635-645
22. Novick, P. A., Lopes, D. H., Branson, K. M., Esteras-Chopo, A., Graef, I. A., Bitan, G., and Pande, V. S. (2012) Design of β-Amyloid Aggregation Inhibitors from a Predicted Structural Motif J. Med. Chem. 55, 3002-3010
23. Carlson, H. A. (2002) Protein flexibility and drug design: how to hit a moving target Curr. Opin. Chem. Biol. 6, 447-452
24. Verkhivker, G. M., Bouzida, D., Gehlhaar, D. K., Rejto, P. A., Freer, S. T., and Rose, P. W. (2002) Complexity and simplicity of ligand-macromolecule interactions: the energy landscape perspective Curr. Opin. Struct. Biol. 12, 197-203
25. Tuffery, P. and Derreumaux, P. (2012) Flexibility and binding affinity in protein-ligand, protein-protein and multi-component protein interactions: limitations of current computational approaches J. R. Soc. London Interface 9, 20-33
26. Yang, M. and Teplow, D. B. (2008) Amyloid β-Protein Monomer Folding: Free-Energy Surfaces Reveal Alloform-Specific Differences J. Mol. Biol. 384, 450-464
27. Karplus, M. and Petsko, G. A. (1990) Molecular dynamics simulations in biology Nature 347, 631-639
28. Karplus, M. and McCammon, J. A. (2002) Molecular dynamics simulations of biomolecules Nat. Struct. Biol. 9, 646-652
29. Brooks, C. L., III (1998) Simulations of protein folding and unfolding Curr. Opin. Struct. Biol. 8, 222-226
30. Urbanc, B., Cruz, L., Teplow, D. B., and Stanley, H. E. (2006) Computer Simulations of Alzheimers Amyloid β-Protein Folding and Assembly Curr. Alzheimer Res. 3, 493-504
31. Cornell, W. D., Cieplak, P., Bayly, C. I., Gould, I. R., Merz, K. R., Jr., Ferguson, D. M., Spellmeyer, D. C., Fox, T., Caldwell, J. W., and Kollman, P. A. (1995) A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules J. Am. Chem. Soc. 117, 5179-5197
32. Wang, J., Cieplak, P., and Kollman, P. A. (2000) How Well Does a Restrained Electrostatic Potential (RESP) Model Perform in Calculating Conformational Energies of Organic and Biological Molecules? J. Comput. Chem. 21, 1049-1074
33. Duan, Y., Wu, C., Chowdhury, S., Lee, M. C., Xiong, G., Zhang, W., Yang, R., Cieplak, P., Luo, R., Lee, T., Caldwell, J., Wang, J., and Kollman, P. (2003) A Point-Charge Force Field for Molecular Mechanics Simulations of Proteins Based on Condensed-Phase Quantum Mechanical Calculations J. Comput. Chem. 24, 1999-2012
34. Sorin, E. J. and Pande, V. S. (2005) Exploring the Helix-Coil Transition via All-Atom Equilibrium Ensemble Simulations Biophys. J. 88, 2472-2493
35. Lindorff-Larsen, K., Piana, S., Palmo, K., Maragakis, P., Klepeis, J. L., Dror, R. O., and Shaw, D. E. (2010) Improved side-chain torsion potentials for the Amber ff99SB protein force field Proteins 78, 1950-1958
36. Hornak, V., Abel, R., Okur, A., Strockbine, B., Roitberg, A., and Simmerling, C. (2006) Comparison of Multiple Amber Force Fields and Development of Improved Protein Backbone Parameters Proteins 65, 712-725
37. MacKerell, A. D., Jr., Bashford, D., Bellot, M., Dunbrack, R. L., Jr., Evanseck, J. D., Field, M. J., Fischer, S., Gao, J., Guo, H., Ha, S., Joseph-McCarthy, D., Kuchnir, L., Kuczera, K., Lau, F. T. K., Mattos, C., Michnick, S., Ngo, T., Nguyen, D. T., Prodhom, B., Reiher, W. E., III, Roux, B., Schlenkrich, M., Smith, J. C., Stote, R., Straub, J., Watanabe, M., Wiórkiewicz-Kuczera, J., Yin, D., and Karplus, M. (1998) All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins J. Phys. Chem. B 102, 3586-3616
38. MacKerell, A. D., Jr., Feig, M., and Brooks, C. L., III (2004) Extending the treatment of backbone energetics in protein force fields: Limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations J. Comput. Chem. 25, 1400-1415
39. Foloppe, N. and MacKerell, A. D., Jr. (2000) All-Atom Empirical Force Field for Nucleic Acids: I. Parameter Optimization Based on Small Molecule and Condensed Phase Macromolecular Target Data J. Comput. Chem. 21, 86-104
40. MacKerell, A. D., Jr., Banavali, N., and Foloppe, N. (2001) Development and Current Status of the CHARMM Force Field for Nucleic Acids Biopolymers 56, 257-265
41. Feller, S. E. and MacKerell, A. D., Jr. (2000) An Improved Empirical Potential Energy Function for Molecular Simulations of Phospholipids J. Phys. Chem. B 104, 7510-7515
42. Feller, S. E., Gawrisch, K., and MacKerell, A. D., Jr. (2002) Polyunsaturated Fatty Acids in Lipid Bilayers: Intrinsic and Environmental Contributions to Their Unique Physical Properties J. Am. Chem. Soc. 124, 318-326
43. Klauda, J. B., Brooks, B. R., MacKerell, A. D., Jr., Venable, R. M., and Pastor, R. W. (2005) An ab Initio Study on the Torsional Surface of Alkanes and Its Effect on Molecular Simulations of Alkanes and a DPPC Bilayer J. Phys. Chem. B 109, 5300-5311
44. Guvench, O., Greene, S. N., Kamath, G., Brady, J. W., Venable, R. M., Pastor, R. W., and MacKerell, A. D., Jr. (2008) Additive Empirical Force Field for Hexopyranose Monosaccharides J. Comput. Chem. 29, 2543-2564
45. van Gunsteren, W. F. and Berendsen, H. J. C. (1987) Groningen Molecular Simulation (GROMOS) Library Manual, BIOMOS b.v., Groningen.
46. van Gunsteren, W. F., Billeter, S. R., Eising, A. A., Hunenberger, P. H., Kruger, P., Mark, A. E., Scott, W. R. P., and Tironi, I. G. (1996) Biomolecular Simulation: The GROMOS96 Manual and User Guide, vdf Hochschulverlag AG an der ETH Zurich and BIOMOS b.v., Zurich, Groningen.
47. Schuler, L. D. and van Gunsteren, W. F. (2000) On the choice of dihedral angle potential energy functions for n-alkanes Mol. Sim. 25, 301-319
48. Schuler, L. D., Daura, X., and van Gunsteren, W. F. (2001) An Improved GROMOS96 Force Field for Aliphatic Hydrocarbons in the Condensed Phase J. Comput. Chem. 22, 1205-1218
49. Oostenbrink, C., Villa, A., Mark, A. E., and van Gunsteren, W. F. (2004) A Biomolecular Force Field Based on the Free Enthalpy of Hydration and Solvation: The GROMOS Force-Field Parameter Sets 53A5 and 53A6 J. Comput. Chem. 25, 1656-1676
50. Jorgensen, W. L., Maxwell, D. S., and Tirado-Rives, J. (1996) Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids J. Am. Chem. Soc. 118, 11225-11236
51. Kaminski, G. A., Friesner, R. A., Tirado-Rives, J., and Jorgensen, W. L. (2001) Evaluation and Reparameterization of the OPLS-AA Force Field for Proteins via Comparison with Accurate Quantum Chemical Calculations on Peptides J. Phys. Chem. B 105, 6474-6487
52. Maupetit, J., Tuffery, P., and Derreumaux, P. (2007) A coarse-grained protein force field for folding and structure prediction Proteins 69, 394-408
53. Marrink, S.-J., Risselada, H. J., Yefimov, S., Tieleman, D. P., and de Vries, A. H. (2007) The MARTINI: Force Field: Coarse Grained Model for Biomolecular Simulations J. Phys. Chem. B 111, 7812-7824
54. Monticelli, L., Kandasamy, S. K., Periole, X., Larson, R. G., Tieleman, D. P., and Marrink, S.-J. (2008) The MARTINI Coarse-Grained Force Field: Extension to Proteins J. Chem. Theory Comput. 4, 819-834
55. 1-40(D23N) J. Phys. Chem. B 116, 4043-4055
56. Chebaro, Y., Mousseau, N., and Derreumaux, P. (2009) Structures and Thermodynamics of Alzheimers Amyloid-β Aβ(16-35) Monomer and Dimer by Replica Exchange Molecular Dynamics Simulations: Implications for Full-Length Aβ Fibrillation J. Phys. Chem. B 113, 7668-7675
57. Lu, Y., Wei, G., and Derreumaux, P. (2011) Effects of G33A and G33I Mutations on the Structures of Monomer and Dimer of the Amyloid-β Fragment 29-42 by Replica Exchange Molecular Dynamics Simulations J. Phys. Chem. B 115, 1282-1288
58. Melquiond, A., Dong, X., Mousseau, N., and Derreumaux, P. (2008) Role of the Region 23-28 in Aβ Fibril Formation: Insights from Simulations of the Monomers and Dimers of Alzheimers Peptides Aβ40 and Aβ42 Curr. Alzheimer Res. 5, 244-250
59. Seo, M., Rauscher, S., Pomès, R., and Tieleman, D. P. (2012) Improving Internal Peptide Dynamics in the Coarse-Grained MARTINI Model: Toward Large-Scale Simulations of Amyloid- and Elastin-like Peptides J. Chem. Theory Comput. 8, 1774-1785
60. Teper, G. L., Lecanu, L., Greeson, J., and Papadopoulos, V. (2005) Methodology for Multi-Site Ligand-Protein Docking Identification Developed for the Optimization fo Spirostenol Inhibition of β-Amloid-Induced Neurotoxicity Chem. Biodiversity 2, 1571-1579
61. Braymer, J. J., Choi, J.-S., DeToma, A. S., Wang, C., Nam, K., Kampf, J. W., Ramamoorthy, A., and Lim, M. H. (2011) Development of Bifunctional Stilbene Derivatives for Targeting and Modulating Metal-Amyloid-β Species Inorg. Chem. 50, 10724-10734
62. Wang, Y., Xia, Z., Xu, J.-R., Wang, Y.-X., Hou, L.-N., Qiu, Y., and Chen, H.-Z. (2012) α-Mangostin, a polyphenolic xanthone derivative from mangosteen, attenuates β-amyloid oligomers-induced neurotoxicity by inhibiting amyloid aggregation Neuropharmacology 62, 871-881
63. Yang, C., Zhu, X., Li, J., and Shi, R. (2010) Exploration of the mechanism for LPFFD inhibiting the formation of β-sheet conformation of Aβ(1-42) in water J. Mol. Model. 16, 813-821
64. Liu, D., Xu, Y., Feng, Y., Liu, H., Shen, X., Chen, K., Ma, J., and Jiang, H. (2006) Inhibitor Discovery Targeting the Intermediate Structure of the β-Amyloid Peptide on the Conformational Transition Pathway: Implications in the Aggregation Mechanism of β-Amyloid Peptide Biochemistry 45, 10963-10972
65. Viet, M. H., Ngo, S. T., Lam, N. S., and Li, M. S. (2011) Inhibition of Aggregation of Amyloid Peptides by Beta-Sheet Breaker Peptides and Their Binding Affinity J. Phys. Chem. B 115, 7433-7446
66. Chimon, S. and Ishii, Y. (2005) Capturing Intermediate Structures of Alzheimers β-Amyloid, Aβ(1-40), by Solid-State NMR Spectroscopy J. Am. Chem. Soc. 127, 13472-13473
67. Coles, M., Bicknell, W., Watson, A. A., Fairlie, D. P., and Craik, D. J. (1998) Solution Structure of Amyloid β-Peptide(1-40) in a Water-Micelle Environment. Is the Membrane-Spanning Domain Where We Think It Is? Biochemistry 37, 11064-11077
68. Zhang, S., Iwata, K., Lachenmann, M. J., Peng, J. W., Li, S., Stimson, E. R., Lu, Y.-a., Felix, A. M., Maggio, J. E., and Lee, J. P. (2000) The Alzheimers Peptide Aβ Adopts a Collapsed Coil Structure in Water J. Struct. Biol. 130, 130-141
69. Soto, C., Castaño, E. M., Frangione, B., and Inestrosa, N. C. (1995) The α-Helical to β-Strand Transition in the Amino-terminal Fragment of the Amyloid β-Peptide Modulates Amyloid Formation J. Biol. Chem. 270, 3063-3067
70. Sticht, H., Bayer, P., Willbold, D., Dames, S., Hilbich, C., Beyreuther, K., Frank, R. W., and Rosch, P. (1995) Structure of amyloid A4-(1-40)-peptide of Alzheimers disease Eur. J. Biochem. 233, 293-298
71. Luttmann, E. and Fels, G. (2006) All-atom molecular dynamics studies of the full-length β-amyloid peptides Chem. Phys. 323, 138-147
72. Flock, D., Colacino, S., Colombo, G., and Di Nola, A. (2006) Misfolding of the Amyloid β-protein: A Molecular Dynamics Study Proteins 62, 183-192
73. Sgourakis, N. G., Yan, Y., McCallum, S. A., Wang, C., and Garcia, A. E. (2007) The Alzheimers Peptides Aβ40 and 42 Adopt Distinct Conformations in Water: A Combined MD/NMR Study J. Mol. Biol. 368, 1448-1457
74. Sgourakis, N. G., Merced-Serrano, M., Boutsidis, C., Drineas, P., Du, Z., Wang, C., and Garcia, A. E. (2011) Atomic-Level Characterization of the Ensemble of the Aβ(1-42) Monomer in Water Using Unbiased Molecular Dynamics Simulations and Spectral Algorithms J. Mol. Biol. 405, 570-583
75. Lee, C. and Ham, S. (2011) Characterizing Amyloid-Beta Protein Misfolding From Molecular Dynamics Simulations With Explicit Water J. Comput. Chem. 32, 349-355
76. Velez-Vega, C. and Escobedo, F. A. (2011) Characterizing the Structural Behavior of Selected Aβ-42 Monomers with Different Solubilities J. Phys. Chem. B 115, 4900-4910
77. 1-42 as Influenced by pH and a D-Peptide J. Phys. Chem. B 116, 3280-3291
78. Petkova, A. T., Yau, W.-M., and Tycko, R. (2006) Experimental Constraints on Quaternary Structure in Alzheimers β-Amyloid Fibrils Biochemistry 45, 498-512
79. Paravastu, A. K., Leapman, R. D., Yau, W.-M., and Tycko, R. (2008) Molecular structural basis for polymorphism in Alzheimers β-amyloid fibrils Proc. Natl. Acad. Sci. U.S.A. 105, 18349-18354
80. Luhrs, T., Ritter, C., Adrian, M., Riek-Loher, D., Bohrmann, B., Dobeli, H., Schubert, D., and Riek, R. (2005) 3D structure of Alzheimers amyloid-β(1-42) fibrils Proc. Natl. Acad. Sci. U.S.A. 102, 17342-17347
81. Chen, D., Martin, Z. S., Soto, C., and Schein, C. H. (2009) Computational selection of inhibitors of Aβ aggregation and neuronal toxicity Biorg. Med. Chem. 17, 5189-5197
82. Yang, Y., Zhu, L., Chen, X., and Zhang, H. (2010) Binding research on flavones as ligands of β-amyloid aggregates by fluorescence and their 3D-QSAR, docking studies J. Mol. Graphics Modell. 29, 538-545
83. Keshet, B., Gray, J. J., and Good, T. A. (2010) Structural distinct toxicity inhibitors bind at common loci on β-amyloid fibril Protein Sci. 19, 2291-2304
84. Morris, G. M., Goodsell, D. S., Halliday, R. S., Huey, R., Hart, W. E., Belew, R. K., and Olson, A. J. (1998) Automated Docking Using a Lamarckian Genetic Algorithm and an Empirical Binding Free Energy Function J. Comput. Chem. 19, 1639-1662
85. Trott, O. and Olson, A. J. (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading J. Comput. Chem. 31, 455-461
86. Reynolds, C. H. and Holloway, M. K. (2011) Thermodynamics of ligand binding and efficiency ACS Med. Chem. Lett. 2, 433-437
87. Roychaudhuri, R., Yang, M., Hoshi, M. M., and Teplow, D. B. (2009) Amyloid β-Protein Assembly and Alzheimer Disease J. Biol. Chem. 284, 4749-4753
88. 1-40(D23N) J. Chem. Theory Comput. 7, 2584-2592
89. Xu, Y., Shen, J., Luo, X., Zhu, W., Chen, K., Ma, J., and Jiang, H. (2005) Conformational transition of amyloid β-peptide Proc. Natl. Acad. Sci. U.S.A. 102, 5403-5407
90. Zhao, L. N., Chiu, S.-W., Benoit, J., Chew, L. Y., and Mu, Y. (2011) Amyloid β Peptides Aggregation in a Mixed Membrane Bilayer: A Molecular Dynamics Study J. Phys. Chem. B 115, 12247-12256
91. Davis, C. H. and Berkowitz, M. L. (2009) Interaction Between Amyloid-β (1-42) Peptide and Phospholipid Bilayers: A Molecular Dynamics Study Biophys. J. 96, 785-797
92. Davis, C. H. and Berkowitz, M. L. (2009) Structure of the Amyloid-β (1-42) Monomer Absorbed To Model Phospholipid Bilayers: A Molecular Dynamics Study J. Phys. Chem. B 113, 14480-14486
93. Davis, C. H. and Berkowitz, M. L. (2010) A molecular dynamics study of the early stages of amyloid-β(1-42) oligomerization: The role of lipid membranes Proteins 78, 2533-2545
94. Miyashita, N., Straub, J. E., and Thirumalai, D. (2009) Structures of the β-Amyloid Peptide 1-40, 1-42, and 1-55-the 672-726 Fragment of APP-in a Membrane Environment with Implications for Interactions with γ-Secretase J. Am. Chem. Soc. 131, 17843-17852
95. Qiu, L., Buie, C., Reay, A., Vaughn, M. W., and Cheng, K. H. (2011) Molecular Dynamics Simulations Reveal the Protective Role of Cholesterol in β-Amyloid Protein-Induced Membrane Disruptions in Neuronal Membrane Mimics J. Phys. Chem. B 115, 9795-9812
96. Lemkul, J. A. and Bevan, D. R. (2008) A comparative molecular dynamics analysis of the amyloid β-peptide in a lipid bilayer Arch. Biochem. Biophys. 470, 54-63
97. Lemkul, J. A. and Bevan, D. R. (2009) Perturbation of membranes by the amyloid β-peptide-a molecular dynamics study FEBS J. 276, 3060-3075
98. Lemkul, J. A. and Bevan, D. R. (2011) Lipid composition influences the release of Alzheimers amyloid β-peptide from membranes Protein Sci. 20, 1530-1545
99. Convertino, M., Pellarin, R., Catto, M., Carotti, A., and Caflisch, A. (2009) 9,10-Anthraquinone hinders β-aggregation: How does a small molecule interfere with Aβ-peptide amyloid fibrillation Protein Sci. 18, 792-800
100. Convertino, M., Vitalis, A., and Caflisch, A. (2011) Disordered Binding of Small Molecules to Aβ(12-28) J. Biol. Chem. 286, 41578-41588
101. Liu, F.-F., Ji, L., Dong, X.-Y., and Sun, Y. (2009) Molecular Insight into the Inhibition Effect of Trehalose on the Nucleation and Elongation of Amyloid β-Peptide Oligomers J. Phys. Chem. B 113, 11320-11329
102. 16-22 Peptide Probed by Molecular Dynamics Simulations J. Mol. Biol. 384, 718-729
103. 42- Induced Toxicity J. Am. Chem. Soc. 133, 4348-4358
104. Gordon, D. J., Sciarretta, K. L., and Meredith, S. C. (2001) Inhibition of β-Amyloid(40) Fibrillogenesis and Disassembly of β-Amyloid(40) Fibrils by Short β-Amyloid Congeners Containing N- Methyl Amino Acids at Alternate Residues Biochemistry 40, 8237-8245
105. Gordon, D. J., Tappe, R., and Meredith, S. C. (2002) Design and characterization of a membrane permeable N- methyl amino acid-containing peptide that inhibits Aβ1-40 fibrillogenesis J. Pept. Sci. 60, 37-55
106. Sciarretta, K. L., Boire, A., Gordon, D. J., and Meredith, S. C. (2006) Spatial Separation of β-Sheet Domains of β-Amyloid: Disruption of Each β-Sheet by N- Methyl Amino Acids Biochemistry 45, 9485-9495
107. Adessi, C., Frossard, M.-J., Boissard, C., Fraga, S., Bieler, S., Ruckle, T., Vilbois, F., Robinson, S. M., Mutter, M., Banks, W. A., and Soto, C. (2003) Pharmacological Profiles of Peptide Drug Candidates for the Treatment of Alzheiemers Disease J. Biol. Chem. 278, 13905-13911
108. Chebaro, Y. and Derreumaux, P. (2009) Targeting the early steps of Aβ16-22 protofibril disassembly by N-methylated inhibitors: A numerical study Proteins 75, 442-452
109. Soto, P., Griffin, M. A., and Shea, J.-E. (2007) New Insights into the Mechanism of Alzheimer Amyloid-β Fibrillogenesis Inhibition by N- Methylated Peptides Biophys. J. 93, 3015-3025
110. Liu, F.-F., Dong, X.-Y., He, L., Middelberg, A. P. J., and Sun, Y. (2011) Molecular Insight into Conformational Transition of Amyloid β-Peptide 42 Inhibited by (-)-Epigallocatechin-3-gallate Probed by Molecular Simulations J. Phys. Chem. B 115, 11879-11887
111. Raman, E. P., Takeda, T., and Klimov, D. K. (2009) Molecular Dynamics Simulations of Ibuprofen Binding to Aβ Peptides Biophys. J. 97, 2070-2079
112. Takeda, T., Kumar, R., Raman, E. P., and Klimov, D. K. (2010) Nonsteroidal Anti-inflammatory Drug Naproxen Destabilizes Aβ Amyloid Fibrils: A Molecular Dynamics Investigation J. Phys. Chem. B 114, 15394-15402
113. Takeda, T., Chang, W. E., Raman, E. P., and Klimov, D. K. (2010) Binding of nonsteroidal anti-inflammatory drugs to Aβ fibril Proteins 78, 2849-2860
114. Chang, W. E., Takeda, T., Raman, E. P., and Klimov, D. K. (2010) Molecular Dynamics Simulations of Anti-Aggregation Effect of Ibuprofen Biophys. J. 98, 2662-2670
115. 42 Protofibrils with Morin: Mechanistic Insights from Molecular Dynamics Simulations Biochemistry 49, 3935-3946
116. Lemkul, J. A. and Bevan, D. R. (2012) Morin Inhibits the Early Stages of Amyloid β-Peptide Aggregation by Altering Tertiary and Quaternary Interactions to Produce Off-Pathway Structures Biochemistry 51, 5990-6009
117. Buchete, N.-V., Tycko, R., and Hummer, G. (2005) Molecular Dynamics Simulations of Alzheimers β-Amyloid Protofilaments J. Mol. Biol. 353, 804-821
118. 17-42 Fibril Architecture: Tight Intermolecular Sheet-Sheet Association and Intramolecular Hydrated Cavities Biophys. J. 93, 3046-3057
119. Perutz, M. F., Finch, J. T., Berriman, J., and Lesk, A. (2002) Amyloid fibers are water-filled nanotubes Proc. Natl. Acad. Sci. U.S.A. 99, 5591-5595
120. Lemkul, J. A. and Bevan, D. R. (2010) Assessing the Stability of Alzheimers Amyloid Protofibrils Using Molecular Dynamics J. Phys. Chem. B 114, 1652-1660
121. Kitchen, D. B., Decornez, H., Furr, J. R., and Bajorath, J. (2004) Docking and scoring in virtual screening for drug discovery: Methods and applications Nat. Rev. Drug Discovery 3, 935-949
122. Leach, A. R., Schoichet, B. K., and Peishoff, C. E. (2006) Prediction of Protein-Ligand Interactions. Docking and Scoring: Successes and Gaps J. Med. Chem. 49, 5851-5855
123. Moitessier, N., Englebienne, P., Lee, D., Lawandi, J., and Corbeil, C. R. (2008) Towards the development of universal, fast and highly accurate docking/scoring methods: a long way to go Br. J. Pharmacol. 153, S7-S26
124. Shan, Y., Kim, E. T., Eastwood, M. P., Dror, R. O., Seeliger, M. A., and Shaw, D. E. (2011) How Does a Drug Molecule Find Its Target Binding SIte? J. Am. Chem. Soc. 133, 9181-9183
125. Shaw, D. E., Dror, R. O., Salmon, J. K., Grossman, J. P., Mackenzie, K. M., Bank, J. A., Young, C., Deneroff, M. M., Batson, B., Bowers, K. J., Chow, E., Eastwood, M. P., Ierardi, D. J., Klepeis, J. L., Kuskin, J. S., Larson, R. H., Lindorff-Larsen, K., Maragakis, P., Moraes, M. A., Piana, S., Shan, Y., and Towles, B. (2009) Millisecond-Scale Molecular Dynamics Simulations on Anton. In Proceedings of the Conference on High Performance Computing, Networking, Storage and Analysis (SC09), ACM, New York.
126. Buch, I., Giorgino, T., and De Fabritiis, G. (2011) Complete reconstruction of an enzyme-inhibitor binding process by molecular dynamics simulations Proc. Natl. Acad. Sci. U.S.A. 108, 10184-10189
127. Rzepiela, A. J., Schafer, L. V., Goga, N., Risselada, H. J., de Vries, A. H., and Marrink, S. J. (2010) Reconstruction of Atomistic Details from Coarse-Grained Structures J. Comput. Chem. 31, 1333-1343
128. Wang, J., Wolf, R. M., Caldwell, J. W., Kollman, P. A., and Case, D. A. (2004) Development and Testing of a General Amber Force Field J. Comput. Chem. 25, 1157-1174
129. Vanommeslaeghe, K., Hatcher, E., Acharya, C., Kundu, S., Zhong, S., Shim, J., Darian, E., Guvench, O., Lopes, P., Vorobyov, I., and MacKerell, A. D., Jr. (2010) CHARMM General Force Field: A Force Field for Drug-Like Molecules Compatible with the CHARMM All-Atom Additive Biological Force Fields J. Comput. Chem. 31, 671-690
130. van Aalten, D. M. F., Bywater, R., Findlay, J. B. C., Hendlich, M., Hooft, R. W. W., and Vriend, G. (1996) PRODRG, a program for generating molecular topologies and unique molecular descriptors from coordinates of small molecules J. Comput.-Aided Mol. Des. 10, 255-262
131. Schuttelkopf, A. W. and van Aalten, D. M. F. (2004) PRODRG: a tool for high-throughput crystallography of protein-ligand complexes Acta Crystallogr., Sect. D: Biol. Crystallogr. 60, 1355-1363
132. Malde, A. K., Zuo, L., Breeze, M., Stroet, M., Poger, D., Nair, P. C., Oostenbrink, C., and Mark, A. E. (2011) An Automated Force Field Topology Builder (ATB) and Repository: Version 1.0 J. Chem. Theory Comput. 7, 4026-4037
133. Lemkul, J. A., Allen, W. J., and Bevan, D. R. (2010) Practical Considerations for Building GROMOS-Compatible Small-Molecule Topologies J. Chem. Inf. Model. 50, 2221-2235
134. Kranjc, A., Bongarzone, S., Rosetti, G., Biarnés, X., Cavalli, A., Bolognesi, M. L., Roberti, M., Legname, G., and Carloni, P. (2009) Docking Ligands on Protein Surfaces: The Case Study of Prion Protein J. Chem. Theory Comput. 5, 2565-2573
135. Chebaro, Y., Jiang, P., Zang, T., Mu, Y., Nguyen, P. H., Mousseau, N., and Derreumaux, P. (2012) Structures of Aβ17-42 Trimers in Isolation and with Five Small-Molecule Drugs Using a Hierarchical Computational Procedure J. Phys. Chem. B 116, 8412-8422
136. Proctor, E. A., Yin, S., Tropsha, A., and Dokholyan, N. V. (2012) Discrete Molecular Dynamics Distinguishes Nativelike Binding Poses from Decoys in Difficult Targets Biophys. J. 102, 144-151
137. Urbanc, B., Cruz, L., Ding, F., Sammond, D., Khare, S., Buldyrev, S. V., Stanley, H. E., and Dokholyan, N. V. (2004) Molecular Dynamics Simulation of Amyloid β Dimer Formation Biophys. J. 87, 2310-2321
138. Urbanc, B., Betnel, M., Cruz, L., Bitan, G., and Teplow, D. B. (2010) Elucidation of Amyloid β-Protein Oligomerization Mechanisms: Discrete Molecular Dynamics Study J. Am. Chem. Soc. 132, 4266-4280
139. 1-42 Toxicity Inhibition by Aβ C-Terminal Fragments: Discrete Molecular Dynamics Study J. Mol. Biol. 410, 316-328