The Cu2*-bound and metal-free cr-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 us. It was found that the Cu2'-bound a-synuclein (1-17) peptide contained more unfluctuating secondary structure samples and more ^-conformations than the metal-free a-synuclein (1-17) peptide. Simulations indicate that the Cu2*-bound a-synuclein (1-17) peptide prefers conformations that allow larger solvent exposure of hydrophobic residues than the metal-free a-synuclein (1-17) peptide, which provides underlying evidence for why Cu2* promotes the aggregation of a-synuclein. By mapping the free energy surface landscape, we found that conformations of Cu2'-bound a-synuclein (1-17) peptide distribute more compactly than the metal-free a-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 a-synuclein from intrinsic disorder to order, which is central to the conformational dynamic and thermodynamic properties of the Cu2*-bound and metal-free a-synuclein (1-17) peptides at the molecular level. This work is propitious to understanding the mechanisms of Cu2' participation in the fibrillization of a-synuclein.%利用分子动力学模拟研究铜离子(Cu2+)对α-突触核蛋白1-17号氨基酸肽段(α-synuclein (1-17))构象变化的影响,采用GROMOS 43A1力场对Cu2+-α-synuclein (1-17)复合体和α-synuclein (1-17)肽段单体分别进行了6组独立的分子动力学模拟,每组模拟时间为500 ns,总模拟时间为3 μs.研究结果表明:Cu2+与α-synuclein (1-17)肽段结合使其更易向β折叠片结构折叠,促进了其二级结构的形成,增强了构象的稳定性;Cu2+增大了α-synuclein肽段疏水残基的溶剂可及表面积,增强了其疏水残基的暴露程度.自由能分析指出,Cu2+-α-synuclein (1-17)复合体的自由能比α-synuclein (1-17)肽段低,构象稳定,采样空间紧密,其自由能极小构象为β折叠片结构.构象聚类分析进一步表明,Cu2+使得α-synuclein (1-17)肽段构象趋于稳定.总之,Cu2+诱导固有无序蛋白α-synuclein (1-17)肽段由无序向有序转变,降低了构象的自由能,同时Cu2+增强了α-synuclein (1-17)肽段的疏水性,使得α-synuclein肽段因疏水作用更倾向于形成β折叠片结构,加速其疏水性聚集.
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