title: Concentration and temperature dependences of polyglutamine aggregation by multiscale coarse-graining molecular dynamics simulations.
abstract: 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.
authors: 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.
authors: Li
authors: L
authors: Deng
authors: Yanting
authors: Y
authors: Wang
authors: Zhong-can
authors: ZC
authors: Ou-yang
mesh_terms: D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000032:analysis* / Q000737:chemistry*; D013696:Temperature
chemical_list: D010455:Peptides; C097188:polyglutamine