EXCERPT OF DISSERTATION Molecular dynamics simulations studies on the structure-function relationship of protein targets related to Alzheimer's disease (Received 2 April 2008) Xu YC, Jiang HL. Molecular dynamics simulations studies on the structure-function relationship of protein targets related to Alzheimer's disease.Journal of the Graduate School of the Chinese Academy of Sciences, 2009, 26(2):280~287

doi:10.7523/j.issn.2095-6134.2009.2.019

Abstract

Abstract:

In the present thesis, the conformational changes of β-amyloid peptide, the dynamic binding and unbinding processes of huperzine A to acetylcholinesterase, and the conformational movement associated with the open or close gating mechanism of nicotinic acetylcholine receptor have been investigated using conventional and/or steered molecular dynamics simulations, gaining new and useful insights for the pathogenetic mechanism of Alzheimer's disease (AD), and providing new clues for discovering new anti-AD drugs.

Key words: Alzheimer ’s disease, molecular dynamics simulation, β-amyloid peptide, ac~ety~lch~oli~nes~ter~ase/huperzine A, nicotinic acetylcholine receptor

CLC Number:

R962

XU Ye-Chun, JIANG Hua-Liang. EXCERPT OF DISSERTATION Molecular dynamics simulations studies on the structure-function relationship of protein targets related to Alzheimer's disease (Received 2 April 2008) Xu YC, Jiang HL. Molecular dynamics simulations studies on the structure-function relationship of protein targets related to Alzheimer's disease.Journal of the Graduate School of the Chinese Academy of Sciences, 2009, 26(2):280~287[J]. , 2009, 26(2): 280-287.

References

[1] Selkoe DJ. The molecular pathology of Alzheimer's disease. Neuron, 1991, 6(4):487~498

[2] Karplus M, McCammon JA. Molecular dynamics simulations of biomolecules. Nat Struct Biol, 2002, 9(9):646~652

[3] Xu YC, Shen JH, Luo XM, et al. Conformational transition of amyloid beta-peptide. Proc Natl Acad Sci USA, 2005, 102(15):5403~5407

[4] Miller DL, Papayannopoulos IA, Styles J, et al. Peptide compositions of the cerebrovascular and senile plaque core amyloid deposits of Alzheimer's disease. Arch Biochem Biophys, 1993, 301(1):41~52

[5] Mattson MP. Cellular actions of β-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol Rev, 1997, 77(4):1081~1132

[6] Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev, 2001, 81(2):741~766

[7] Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science, 2002, 297(5580):353~356

[8] McLean CA, Cherny RA, Fraser FW, et al. Soluble pool of Ab amyloid as a determinant of neurodegeneration in Alzheimer's disease. Ann Neurol, 1999, 46(6):860~866

[9] Walsh DM, Klyubin I, Fadeeva JV, et al. Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo. Nature, 2002, 416(6880):535~539

[10] Rosenblum WI. 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. Neurobiol Aging, 2002, 23(2):225~230

[11] Straub JE, Guevara J, Huo SH, et al. Long time dynamic simulations: exploring the folding pathways of an Alzheimer's amyloid Aβ-peptide. Acc Chem Res, 2002, 35(6):473~481

[12] Hwang W, Zhang S, Kamm RD, et al. Kinetic control of dimer structure formation in amyloid fibrillogenesis. Proc Natl Acad Sci USA, 2004, 101(35):12916~12921

[13] Barrow CJ, Yasuda A, Kenny PTM, et al. Solution conformations and aggregational properties of synthetic amyloid β-peptide of Alzheimer's disease. J Mol Biol, 1992, 225(4):1075~1093

[14] Sunde M, Serpell LC, Bartlam M, et al. Common core structure of amyloid fibrils by synchrotron X-ray diffraction. J Mol Biol, 1997, 273(3):729~739

[15] Teplow DB. Structural and kinetic features of amyloid β-protein fibrillogenesis. Amyloid, 1998, 5(2):121~142

[16] Xu YC, Shen JH, Luo XM, et al. How does Huperzine A enter and leave the binding gorge of acetylcholinesterase? steered molecular dynamics simulations. J Am Chem Soc, 2003, 125(37):11340~11349

[17] Quinn DM. Acetylcholinesterase: enzyme structure, reaction dynamics, and virtual transition state. Chem Rev, 1987, 87(5):955~979

[18] Tang XC, Han YF. Pharmacological profile of huperzine A, a novel acetylcholinesterase inhibitor from chinese herb. CNS Drug Review, 1999, 5(3):281~300

[19] Ashani Y, Peggins Ⅲ JO, Doctor BP. Mechanism of inhibition of cholinesterases by huperzine A. Biochem Biophys Res Comm, 1992, 184(2):7719~7726

[20] Sussman JL, Harel M, Frolow F, et al. Atomic structure of acetylcholinesterase from Torpedo Californica: a arototypic acetylcholine-binding Protein. Science, 1991, 253(5022):872~879

[21] Raves ML, Harel M, Pang YP, et al. Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A. Nat Struct Biol, 1997, 4(1):57~63

[22] Xu YC, Barrantes FJ, Luo XM, et al. Conformational dynamics of the nicotinic acetylcholine receptor channel: a 35ns molecular dynamics simulation study. J Am Chem Soc, 2005, 127(4):1291~1299

[23] Xu YC, Barrantes FJ, Shen JH, et al. Blocking of the nicotinic acetylcholine receptor ion channel by chlorpromazine, a noncompetitive inhibitor: A molecular dynamics simulation study. J Phys Chem B, 2006, 110(41):20640~20648

[24] Xu YC, Luo XM, Shen JH, et al. Molecular dynamics of nicotinic acetylcholine receptor correlating biological functions. Curr Protein Pept Sci, 2006, 7(3):195~200

[25] Karlin A. Emerging structure of the nicotinic acetylcholine receptors. Nat Rev Neurosci, 2002, 3(2):102~114

[26] Miyazawa A, Fujiyoushi Y, Unwin N. Structure and gating mechanism of the acetylcholine receptor pore. Nature, 2003, 423(6943):949~955

[27] Morris GM, Goodsell DS, Halliday RS, et al. Automated docking using a lamarchian genetic algorithm and empirical binding free energy function. J Comp Chem, 1998, 19(14):1639~1662

[28] McCammon JA, Gelin BR, Karplus M. Dynamics of folded proteins. Nature, 1977, 267(5612):585~590

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