title: Capping parallel β-sheets of acetyl(Ala)6NH2 with an acetyl(Ala)5ProNH2 can arrest the growth of the sheet, suggesting a potential for curtailing amyloid growth. An ONIOM and density functional theory study.
abstract: We present ONIOM calculations using B3LYP/d95(d,p) as the high level and AM1 as the medium level on parallel β-sheets containing four strands of Ac-AAAAAA-NH2 capped with either Ac-AAPAAA-NH2 or Ac-AAAPAA-NH2. Because Pro can form H-bonds from only one side of the peptide linkage (that containing the C═O H-bond acceptor), only one of the two Pro-containing strands can favorably add to the sheet on each side. Surprisingly, when the sheet is capped with AAPAAA-NH2 at one edge, the interaction between the cap and sheet is slightly more stabilizing than that of another all Ala strand. Breaking down the interaction enthalpies into H-bonding and distortion energies shows the favorable interaction to be due to lower distortion energies in both the strand and the four-stranded sheet. Because another strand would be inhibited for attachment to the other side of the capping (Pro-containing) strand, we suggest the possible use of Pro residues in peptides designed to arrest the growth of many amyloids.
authors.affiliation: Department of Chemistry, City University of New York, Hunter College and the Graduate School , 695 Park Avenue, New York, New York 10065, United States.
authors.forename: Gabor
authors.initials: G
authors.lastname: Pohl
authors.forename: Amparo
authors.initials: A
authors.lastname: Asensio
authors.forename: J J
authors.initials: JJ
authors.lastname: Dannenberg
mesh_terms: D019943:Amino Acid Substitution; D000682:Amyloid / Q000737:chemistry*; D006860:Hydrogen Bonding; D009154:Mutation; D009842:Oligopeptides / Q000737:chemistry* / Q000235:genetics; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D000682:Amyloid; D009842:Oligopeptides