title: Different nanostructures caused by competition of intra- and inter-β-sheet interactions in hierarchical self-assembly of short peptides.
abstract: To understand how molecular interactions lead to the self-assembly of twisted, helical and flat nanoribbons, we have compared the hierarchical self-assembly processes of three selected octapeptides with the same amino acid composition but different sequences by both experiments and molecular dynamics (MD) simulations. KE-F8 (NH2-KEFFFFKE-CONH2) and EK-F8 (NH2-KEFFFFEK-CONH2) have the same distribution of hydrophobic residues and only differ by swapping the positive and negative charged residues at their C-terminals, while KFE-8 (NH2-KFEFKFEF-CONH2) differs from KE-F8 and EK-F8 by having all hydrophobic and charged residues evenly distributed. MD simulations indicated that the competition between electrostatic and hydrophobic interactions at the molecular level results in different initial packing modes: KE-F8 monomers form completely matched anti-parallel β-sheets, EK-F8 monomers align with one residue shifting, and KFE-8 monomers pack β-sheets with two heterogeneous surfaces, consistent with previously suggested models. Driven by inter-strand and inter-sheet interactions, further growth of these molecular templates leads to larger oligomers with different twisting and stacking degrees, which are structurally consistent with the experimentally observed self-assembled morphologies. Further MD simulations showed that the competition between intra-β-sheet and inter-β-sheet interactions is responsible for the different twisting and stacking degrees of β-sheets and the subsequent formation of different nanostructures (twisted ribbons for KE-F8, helical ribbons/tubes for EK-F8 and flat ribbons for KFE-8). This study thus provided an important mechanistic insight into the fine tuning of molecular packing and interactions via peptide sequence variation leading to controllable self-assembly of twisted, helical and flat nanostructures.
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Centre for Bioengineering and Biotechnology, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Centre for Bioengineering and Biotechnology, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China.
authors.forename: Li
authors.initials: L
authors.lastname: Deng
authors.affiliation: 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. Electronic address: wangyt@itp.ac.cn.
authors.forename: Yanting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Biological Physics Group, School of Physics and Astronomy, The University of Manchester, Manchester M13 9PL, United Kingdom. Electronic address: j.lu@manchester.ac.uk.
authors.forename: Jian R
authors.initials: JR
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Centre for Bioengineering and Biotechnology, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China. Electronic address: xuh@upc.edu.cn.
authors.forename: Hai
authors.initials: H
authors.lastname: Xu
mesh_terms: D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D010455:Peptides
keywords: Intermolecular interactions; Molecular dynamics; Molecular packing modes; Nanostructures; Self-assembly; Short peptides