Amphiphilic Peptides A6K and V6K Display Distinct Oligomeric Structures and Self-Assembly Dynamics: A Combined All-Atom and Coarse-Grained Simulation Study

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• 作者：Yunxiang Sun ; Zhenyu Qian ; Cong Guo ; Guanghong Wei
• 刊名：Biomacromolecules
• 出版年：2015
• 出版时间：September 14, 2015
• 年：2015
• 卷：16
• 期：9
• 页码：2940-2949
• 全文大小：538K
• ISSN：1526-4602

文摘

Amphiphilic peptides can self-assemble into ordered nanostructures with different morphologies. However, the assembly mechanism and the structures of the early assemblies prior to nanostructure formation remain elusive. In this study, we investigated the oligomeric structures of two amphiphilic heptapeptides A₆K and V₆K by all-atom explicit-solvent replica-exchange molecular dynamics (REMD) simulations, and then examined the assembly dynamics of large aggregates by coarse-grained (CG) MD simulations. Our 200 ns REMD simulations show that A₆K peptides predominantly adopt loosely packed disordered coil aggregates, whereas V₆K peptides mostly assemble into compact 尾-sheet-rich conformations, consistent with the signal measured experimentally in aqueous solution. Well-organized 尾-sheet-rich conformations, albeit with low population, are also populated for V₆K octamers, including bilayer 尾-sheets and 尾-barrels. These ordered 尾-sheet-rich conformations are observed for the first time for amphiphilic peptides. Our 10-渭s CG-MD simulations on 200 peptide chains demonstrate that A₆K and V₆K peptides follow two different self-assembly processes, and the former form monolayer lamellas while the latter assemble into plate-like assemblies. CG-MD simulations also show that V₆K peptides display higher assembly capability than A₆K, in support of our all-atom REMD simulation results. Interpeptide interaction analyses reveal that the marked differences in oligomeric structures and assembly dynamics between A₆K and V₆K result from the subtle interplay of competition among hydrophobic, hydrogen-bonding, and electrostatic interactions of the two peptides. Our study provides structural and mechanistic insights into the initial self-assembly process of A₆K and V₆K at the molecular level.