title: Fe(2+) binding on amyloid β-peptide promotes aggregation.
abstract: The metal ions Zn(2+) , Cu(2+) , and Fe(2+) play a significant role in the aggregation mechanism of Aβ peptides. However, the nature of binding between metal and peptide has remained elusive; the detailed information on this from the experimental study is very difficult. Density functional theory (dft) (M06-2X/6-311++G (2df,2pd) +LANL2DZ) has employed to determine the force field resulting due to metal and histidine interaction. We performed 200 ns molecular dynamics (MD) simulation on Aβ1-42 -Zn(2+) , Aβ1-42 -Cu(2+) , and Aβ1-42 -Fe(2+) systems in explicit water with different combination of coordinating residues including the three Histidine residues in the N-terminal. The present investigation, the Aβ1-42 -Zn(2+) system possess three turn conformations separated by coil structure. Zn(2+) binding caused the loss of the helical structure of N-terminal residues which transformed into the S-shaped conformation. Zn(2+) has reduced the coil and increases the turn content of the peptide compared with experimental study. On the other hand, the Cu(2+) binds with peptide, β sheet formation is observed at the N-terminal residues of the peptide. Fe(2+) binding is to promote the formation of Glu22-Lys28 salt-bridge which stabilized the turn conformation in the Phe19-Gly25 residues, subsequently β sheets were observed at His13-Lys18 and Gly29-Gly37 residues. The turn conformation facilitates the β sheets are arranged in parallel by enhancing the hydrophobic contact between Gly25 and Met35, Lys16 and Met35, Leu17 and Leu34, Val18 and Leu34 residues. The Fe(2+) binding reduced the helix structure and increases the β sheet content in the peptide, which suggested, Fe(2+) promotes the oligomerization by enhancing the peptide-peptide interaction. Proteins 2016; 84:1257-1274. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Physics, Bharathiar University, Coimbatore, Tamilnadu, 46, India.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Boopathi
authors.affiliation: Department of Physics, Bharathiar University, Coimbatore, Tamilnadu, 46, India.
authors.forename: Ponmalai
authors.initials: P
authors.lastname: Kolandaivel
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002413:Cations, Divalent; D003300:Copper / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007501:Iron / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry*; D066329:Protein Aggregates; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D011789:Quantum Theory; D013816:Thermodynamics; D014867:Water / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D002413:Cations, Divalent; D010446:Peptide Fragments; D066329:Protein Aggregates; C075222:amyloid beta-protein (1-42); D014867:Water; D006639:Histidine; D003300:Copper; D007501:Iron; D015032:Zinc
keywords: Alzheimer's diseases; U-shaped conformation; amyloid β-peptide; metal ions; molecular dynamics simulation