State Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences , 55 East Zhongguancun Road, P.O. Box 2735, Beijing 100190, China.
J Phys Chem B. 2012 Aug 30;116(34):10135-44. doi: 10.1021/jp210683n. Epub 2012 Aug 15.
The solvent-free multiscale coarse-graining model of polyglutamine was employed to study polyglutamine aggregation at different concentrations and temperatures by means of molecular dynamics simulation. The heterogeneity order parameter (HOP) was used to quantify the polyglutamine aggregation. Our simulation results demonstrate that polyglutamine aggregation is sensitive to concentration and temperature changes. In equilibrium states, polyglutamine molecules fluctuate between aggregating tightly and distributing uniformly. The degree of aggregation monotonically increases with decreasing temperature, but the fluctuation of HOP reaches its maximum at an intermediate temperature. With increasing concentration, the distribution of polyglutamines first changes from more uniform to more nonuniform and then changes back to be more uniform, and the HOP has the widest distribution at the turning point. Simulations with different system sizes indicate that the finite-size effect is trivial and do not change the conclusions drawn for the polyglutamine system. In addition, the composition of the potential energies has been analyzed to confirm that the nonbonded interactions dominate the aggregation of polyglutamines. These results can be thermodynamically understood by considering the competition between the system entropy and molecular interactions, and a statistical model based on HOP has been developed to explain the microscopic mechanism of polyglutamine aggregation.
采用无溶剂多尺度粗粒化模型，通过分子动力学模拟研究了不同浓度和温度下的多聚谷氨酰胺聚集。使用不均匀度序参量（HOP）定量多聚谷氨酰胺的聚集。我们的模拟结果表明，多聚谷氨酰胺聚集对浓度和温度变化敏感。在平衡态，多聚谷氨酰胺分子在紧密聚集和均匀分布之间波动。随着温度降低，聚集度单调增加，但 HOP 的波动在中间温度达到最大值。随着浓度增加，多聚谷氨酰胺的分布先是从更均匀变为更不均匀，然后再变回更均匀，在转折点处 HOP 分布最广。不同体系大小的模拟表明，有限尺寸效应微不足道，不会改变对多聚谷氨酰胺体系得出的结论。此外，还分析了势能的组成，以确认非键相互作用主导了多聚谷氨酰胺的聚集。通过考虑系统熵和分子相互作用之间的竞争，可以从热力学上理解这些结果，并基于 HOP 开发了一个统计模型来解释多聚谷氨酰胺聚集的微观机制。
