Molecular Dynamics Simulations of Polyglutamine Aggregation Using Solvent-Free Multiscale Coarse-Grained Models

CORC > 理论物理研究所 > 中国科学院理论物理研究所 > 理论物理所科研产出 > 理论物理所1978-2010年知识产出

	Molecular Dynamics Simulations of Polyglutamine Aggregation Using Solvent-Free Multiscale Coarse-Grained Models
	Wang, Yanting; Voth, Gregory A.; Voth, GA , Univ Chicago, James Franck Inst, Dept Chem, Chicago, IL 60637 USA
刊名	JOURNAL OF PHYSICAL CHEMISTRY B
	2010
卷号	114 期号:26 页码:8735-8743
关键词	Amyloid-like Fibrils Ionic Liquids Huntingtons-disease Neurodegenerative Diseases Monomeric Polyglutamine Potential Functions Lipid-bilayer Peptides Proteins Kinetics
ISSN号	1520-6106
英文摘要	The multiscale coarse-graining (MS-CG) method is used to construct solvent-free CG models for polyglutamine peptides having various repeat lengths. Because the resulting CG models have fewer degrees of freedom than a corresponding all-atom simulations, they make it possible to study the self-assembly of polyglutamines at high concentrations for the first time by allowing for better equilibration and statistical sampling that is well beyond the range achievable by all-atom models. Molecular dynamics (MD) simulations performed with these models show that polyglutamine monomers with repeat lengths <= 28 fluctuate between their folded and unfolded states. Monomers with 32 or more residues are stable and form alpha-helix solid structures. The degree of monomer compactness increases with chain length in both cases. CG MD simulations of equilibrium polyglutamine aggregates show that even at high concentrations, the system statistically fluctuates between heterogeneous and homogeneous configurations, rather than simply aggregates. The degree of aggregation and fluctuation increases with concentration and chain length. All of these phenomena are consistent with the experimental observations and may be explained by a mechanism that the collective nonbonded interactions between polyglutamine molecules in water solution are only weakly attractive. Finally, this work demonstrates that computer simulation of polypeptides self-assembly and aggregation, which is presently beyond the reach of all-atom MD simulations, is attainable using solvent-free MS-CG models.
学科主题	Physics
URL标识	查看原文
WOS记录号	WOS:000279282600018
公开日期	2012-08-02
内容类型	期刊论文
源URL	[http://ir.itp.ac.cn/handle/311006/5079]
专题	理论物理研究所_理论物理所1978-2010年知识产出
通讯作者	Voth, GA , Univ Chicago, James Franck Inst, Dept Chem, Chicago, IL 60637 USA
推荐引用方式 GB/T 7714	Wang, Yanting,Voth, Gregory A.,Voth, GA , Univ Chicago, James Franck Inst, Dept Chem, Chicago, IL 60637 USA. Molecular Dynamics Simulations of Polyglutamine Aggregation Using Solvent-Free Multiscale Coarse-Grained Models[J]. JOURNAL OF PHYSICAL CHEMISTRY B,2010,114(26):8735-8743.
APA	Wang, Yanting,Voth, Gregory A.,&Voth, GA , Univ Chicago, James Franck Inst, Dept Chem, Chicago, IL 60637 USA.(2010).Molecular Dynamics Simulations of Polyglutamine Aggregation Using Solvent-Free Multiscale Coarse-Grained Models.JOURNAL OF PHYSICAL CHEMISTRY B,114(26),8735-8743.
MLA	Wang, Yanting,et al."Molecular Dynamics Simulations of Polyglutamine Aggregation Using Solvent-Free Multiscale Coarse-Grained Models".JOURNAL OF PHYSICAL CHEMISTRY B 114.26(2010):8735-8743.