基于分子动力学模拟研究温度致Aβ42蛋白构象变化
Conformation Transformation of Aβ42 Protein under Different Temperature by Molecular Dynamics Simulations

作者: 付静 * , 赵立岭 * , 王吉华 :德州学院山东省功能大分子生物物理重点实验室,德州;

关键词: Aβ42蛋白分子动力学模拟阿尔兹海默症构象转变Aβ42 Protein Molecular Dynamics Simulation Alzheimer’s Disease Conformation Transformation

摘要:
基于分子动力学模拟方法研究了不同温度对Aβ42蛋白结构的影响。模拟选用GROMACS软件包和GROMOS 43A1分子力场,在300 K、340 K和380 K下分别进行60 ns的分子动力学模拟。通过计算原子均方根涨落、回旋半径、二级结构形成几率等参数,分析了Aβ42蛋白结构的稳定性、二级结构及三级结构形成。研究发现:该蛋白在三种不同温度下,都没有稳定结构,表现出固有无序特征,温度会导致结构特征发生显著变化;在高温(380 K)时,会产生α螺旋向β折叠转换的趋势。

Abstract:
The temperature-induced conformation changes of Aβ42 protein were studied by molecular dynamics simu-lation. The three independent molecular dynamics simulations of Aβ42 protein at different temperatures 300 K, 340 K and 380 K, were performed using the GROMACS software package and GROMOS 43A1 force field, respectively. Each simulation was run for 60 ns. Based on the simulations, we analyzed the conformation changes of Aβ42 protein and the formation of its secondary structure and tertiary structure. The results indicated that Aβ42 protein has no stable structure and it has the characters of intrinsically disorder proteins at the different temperatures. It also shows that the structure of Aβ42 protein change obviously with different temperature. In addition, there is a change tendency from α-helix to β-sheet at 380 K.

文章引用: 付静 , 赵立岭 , 王吉华 (2013) 基于分子动力学模拟研究温度致Aβ42蛋白构象变化。 生物医学, 3, 1-6. doi: 10.12677/HJBM.2013.31001

参考文献

[1] 张伟, 刘志敏. 阿尔茨海默氏症的研究进展[J]. 中国生物工程杂志, 2003, 23(12): 13-16.

[2] R. Nelson, M. R. Sawaya, et al. Structure of the cross-β spine of amyloid-like fibrils. Nature, 2005, 435(7043): 773-778.

[3] 武一, 吉尚戎, 蒋伍玲等. β淀粉样蛋白Aβ1-40和Aβ1-42的聚集性质比较[J]. 电子显微学报, 2003, 22(1): 21-25.

[4] 于双妮, 刘立颖, 梁平作. β-淀粉样蛋白在阿尔茨海默病发病和免疫治疗中的作用[J]. 中国病理学杂志, 2005, 34(2): 113- 114.

[5] T. Takeda, D. K. Klimov. Temperature-induced dissociation of Aβ monomers from amyloid fibril. Biophysical Journal, 2008, 95(4): 1758-1772.

[6] Z. X. Cao, L. Liu, L. L. Zhao, et al. Effects of different force fields and temperatures on the structural character of abeta (12 - 28) peptide in aqueous solution. International Journal of Mo-lecular Sciences, 2011, 12(11): 8259-8274.

[7] Y. Xu, J. Shen, X. Luo, et al. Conformational transition of amy-loid beta-peptide. Proceedings of the National Academy of Sci-ences of the United States of America, 2005, 102(15): 5403- 5407.

[8] G. Wei, A. I. Jewett and J. E. Shea. Structural diversity of dimers of the Alzheimer amyloid-beta (25 - 35) peptide and polymor-phism of the resulting fibrils. Physical Chemistry Chemical Physics, 2010, 12(14): 3622-3629.

[9] D. J. Selkoe. Ahheimer’s disease: Genes, proteins and therapy. Physiological Reviews, 2001, 81(2): 741-766.

[10] K. A. Coalier, G. S. Paranjape, S. Karki, et al. Stability of early-stage amyloid-β(1-42) aggregation species. Biochimica et Biophysica Acta (BBA)—Proteins and Proteomics, 2012, 1834(1): 65-70.

[11] T. Zhao, Y. Zeng and A. R. Kermode. A plant cell-based system that predicts Aβ42 misfolding: Potential as a drug discovery tool for Alzheimer’s disease. Molecular Genetics and Metabolism, 2012, 107(3): 571-579.

[12] 董晓燕, 都文婕, 刘夫锋. 多肽抑制剂抑制淀粉质多肽42构象转换的分子动力学模拟和结合自由能计算[J]. 物理化学学报, 2012, 28(11): 2735-2744.

[13] O. Crescenzi, S. Tomaselli, R. Guerrini, et al. Solution structure of the Alzheimer amyloid beta-peptide (1-42) in an apolar mi-croenvironment. Similarity with a virus fusion domain. Euro-pean Journal of Biochemistry, 2002, 269(22): 5642-5648.

[14] D. van der Spoel, R. van Drunen and H. J. C. Berendsen. Gron-ingen machine for chemical simulations. Groningen: Department of Biophysical Chemistry, BIOSON Research Institute, 1994.

[15] X. Daura, A. E. Mark and W. F. van Gunsteren. Parametrization of aliphatic CHn united atoms of GROMOS96 force field. Jour-nal of Computational Chemistry, 1998, 19: 535-547.

[16] J.-P. Ryckaert, G. Ciccotti and H. J. C. Berendsen. Numerical integration of the Cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. Journal of Com-putational Physics, 1977, 23(3): 327-341.

[17] H. J. C. Berendsen, J. P. M. Postma, W. F. van Gunsteren, et al. Molecular dynamics with coupling to an external bath. Journal of Computational Physics, 1984, 81(8): 3684-3690.

[18] S. H. Chong, S. Ham. Impact of chemical heterogeneity on protein self-assembly in water. Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(20): 7636-7641.

[19] M. Heinig, D. Frishman. STRIDE: A web server for secondary structure assignment from known atomic coordinates of proteins. Nucleic Acids Research, 2004, 32(Web Server Issue): W500- W502.

[20] 许朝莹, 赵立岭, 曹赞霞等. 残基突变对P53-DNA结合域肽段构象影响的分子动力学模拟[J]. 物理化学学报, 2012, 28 (7): 1665-1675.

分享
Top