Self-Assembled Micellar Structures of Lipopeptides with Variable Number of Attached Lipid Chains Revealed by Atomistic Molecular Dynamics Simulations

doi:10.1021/acs.jpcb.8b07877

CORC > 上海应用物理研究所 > 中国科学院上海应用物理研究所 > 中科院上海应用物理研究所2011-2017年

	Self-Assembled Micellar Structures of Lipopeptides with Variable Number of Attached Lipid Chains Revealed by Atomistic Molecular Dynamics Simulations
	Zhao, L ; Tu, YS ; Fang, HP ; Hamley, IW ; Wang, ZW
刊名	JOURNAL OF PHYSICAL CHEMISTRY B
	2018
卷号	122 期号:41 页码:9605-9615
关键词	PEPTIDE-AMPHIPHILE NANOFIBERS PARTICLE MESH EWALD RECEPTOR FAMILY FORCE-FIELD WATER TRANSITIONS PROTEINS SYSTEMS
ISSN号	1520-6106
DOI	10.1021/acs.jpcb.8b07877
文献子类	期刊论文
英文摘要	We present atomistic molecular dynamics simulation study of the self-assembly behavior of toll-like agonist lipopeptides (Pam(n)CSK4) in aqueous solutions. The variable number of hexadecyl lipid chains (n = 1, 2, 3) per molecule has been experimentally suggested to have remarkable influence on their self-assembled nanostructures. Starting from preassembled spherical or bilayer configurations, the aggregates of lipopeptides, PamCSK4 and Pam(2)CSK4, which contain peptide sequences CSK4 linked to either mono- or dilipid chains (Pam), evolve into spherical-like micelles within 30 ns, whereas the self-assembled structure of trilipidated lipopeptides, Pam(3)CSK4, relaxes much slower and reaches an equilibrium state of flattened wormlike micelle with a bilayer packing structure. The geometric shapes and sizes, namely the gyration radii of spherical micelles and thickness of the flattened wormlike micelle, are found to be in good agreement with experimental measurements, which effectively validates the simulation models and employed force fields. Detailed analyses of molecular packing reveal that these self-assembled nanostructures all consist of a hydrophobic core constructed of lipid chains, a transitional layer, and a hydrophilic interfacial layer composed of peptide sequences. The average area per peptide head at the interfaces is found to be nearly constant for all micellar structures studied. The packing parameter of the lipopeptide molecules thus increases with the increase of the number of linked lipid chains, giving rise to the distinct micellar shape transition from spherical-like to flattened wormlike geometry with bilayer stacking, which is qualitatively different from the shape transitions of surfactant micelles induced by variation of concentration or salt type. To facilitate the closepacking of the lipid chains in the hydrophobic core, the lipopeptide molecules typically take the bent conformation with average tilt angles between the peptide sequences and the lipid chains ranging from 110 degrees to 140 degrees. This consequently affects the orientation angles of the lipid chains with respect to the radial or normal direction of the spherical-like or flattened wormlike micelles. In addition, the secondary structures of the peptides may also be altered by the number of lipid chains to which they are linked and the resultant micellar structures. Our simulation results on the microscopic structural features of the lipopeptide nanostructures may provide potential insights into their bioactivities and contribute to the design of bioactive medicines or drug carriers. The force fields built for these lipopeptides and the geometric packing discussions could also be adopted for simulating and understanding the self-assembly behavior of other bioactive amiphiphiles with similar chemical compositions.
语种	英语
内容类型	期刊论文
源URL	[http://ir.sinap.ac.cn/handle/331007/31100]
专题	上海应用物理研究所_中科院上海应用物理研究所2011-2017年
作者单位	1.Univ Reading, Sch Math Phys & Computat Sci, Reading RG6 6AX, Berks, England 2.Yangzhou Univ, Coll Phys Sci & Technol, Yangzhou 225009, Jiangsu, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Appl Phys, Div Interfacial Water, Shanghai 201800, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Appl Phys, Key Lab Interfacial Phys & Technol, Shanghai 201800, Peoples R China 5.Univ Reading, Dept Chem, Reading RG6 6AD, Berks, England
推荐引用方式 GB/T 7714	Zhao, L,Tu, YS,Fang, HP,et al. Self-Assembled Micellar Structures of Lipopeptides with Variable Number of Attached Lipid Chains Revealed by Atomistic Molecular Dynamics Simulations[J]. JOURNAL OF PHYSICAL CHEMISTRY B,2018,122(41):9605-9615.
APA	Zhao, L,Tu, YS,Fang, HP,Hamley, IW,&Wang, ZW.(2018).Self-Assembled Micellar Structures of Lipopeptides with Variable Number of Attached Lipid Chains Revealed by Atomistic Molecular Dynamics Simulations.JOURNAL OF PHYSICAL CHEMISTRY B,122(41),9605-9615.
MLA	Zhao, L,et al."Self-Assembled Micellar Structures of Lipopeptides with Variable Number of Attached Lipid Chains Revealed by Atomistic Molecular Dynamics Simulations".JOURNAL OF PHYSICAL CHEMISTRY B 122.41(2018):9605-9615.