Citation: CAO Jian, CAO Zan-Xia, ZHAO Li-Ling, WANG Ji-Hua. Effect of α-Synuclein (1-17) Peptide for Cu²⁺-Bound and Metal-Free Forms by Molecular Dynamics Simulations[J]. Acta Physico-Chimica Sinica, ;2012, 28(02): 479-488. doi: 10.3866/PKU.WHXB201111231 shu

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

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 Date: 19 September 2011
Available Online: 23 November 2011
Fund Project: 国家自然科学基金(30970561, 31000324)资助项目 (30970561, 31000324)

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.
- Molecular dynamics simulations,
- Cu²⁺-α-synuclein,
- Secondary structure,
- Free energy,
- Fibrotic aggregation
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Effect of α-Synuclein (1-17) Peptide for Cu2+-Bound and Metal-Free Forms by Molecular Dynamics Simulations

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