Acta Phys. -Chim. Sin. ›› 2012, Vol. 28 ›› Issue (02): 479-488.doi: 10.3866/PKU.WHXB201111231

• BIOPHYSICAL CHEMISTRY • Previous Articles     Next Articles

Effect of α-Synuclein (1-17) Peptide for Cu2+-Bound and Metal-Free Forms by Molecular Dynamics Simulations

CAO Jian1,2, CAO Zan-Xia1, ZHAO Li-Ling1, WANG Ji-Hua1   

  1. 1. Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics, Dezhou University, Dezhou 253023, Shandong Province, P. R. China;
    2. College of Physics and Electronics Science, Shandong Normal University, Jinan 250014, P. R. China
  • Received:2011-09-19 Revised:2011-11-09 Published:2012-01-11
  • Contact: WANG Ji-Hua
  • Supported by:

    The project was supported by the National Natural Science Foundation of China (30970561, 31000324).

Abstract: The Cu2+-bound and metal-free α-synuclein (1-17) peptides were simulated with the GROMOS 43A1 force field in the GROMACS package. There were six groups and each group was run for 500 ns in the physiological environment, giving a total of 3 μs. It was found that the Cu2+-bound α-synuclein (1-17) peptide contained more unfluctuating secondary structure samples and more β-conformations than the metal-free α-synuclein (1-17) peptide. Simulations indicate that the Cu2+-bound α-synuclein (1-17) peptide prefers conformations that allow larger solvent exposure of hydrophobic residues than the metal-free α-synuclein (1-17) peptide, which provides underlying evidence for why Cu2+ promotes the aggregation of α-synuclein. By mapping the free energy surface landscape, we found that conformations of Cu2+-bound α-synuclein (1-17) peptide distribute more compactly than the metal-free α-synuclein (1-17) peptide. The results are almost the same as the central conformation obtained by conformational clustering analysis. These new findings indicate that Cu2+ modulates the conformation of α-synuclein from intrinsic disorder to order, which is central to the conformational dynamic and thermodynamic properties of the Cu2+-bound and metal-free α-synuclein (1-17) peptides at the molecular level. This work is propitious to understanding the mechanisms of Cu2+ participation in the fibrillization of α-synuclein.

Key words: Molecular dynamics simulations, Cu2+-α-synuclein, Secondary structure, Free energy, Fibrotic aggregation


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