title: Short peptide amyloid organization: stabilities and conformations of the islet amyloid peptide NFGAIL.
abstract: Experimentally, short peptides have been shown to form amyloids similar to those of their parent proteins. Consequently, they present useful systems for studies of amyloid conformation. Here we simulate extensively the NFGAIL peptide, derived from the human islet amyloid polypeptide (residues 22-27). We simulate different possible strand/sheet organizations, from dimers to nonamers. Our simulations indicate that the most stable conformation is an antiparallel strand orientation within the sheets and parallel between sheets. Consistent with the alanine mutagenesis, we find that the driving force is the hydrophobic effect. Whereas the NFGAIL forms stable oligomers, the NAGAIL oligomer is unstable, and disintegrates very quickly after the beginning of the simulation. The simulations further identify a minimal seed size. Combined with our previous simulations of the prion-derived AGAAAAGA peptide, AAAAAAAA, and the Alzheimer Abeta fragments 16-22, 24-36, 16-35, and 10-35, and the solid-state NMR data for Abeta fragments 16-22, 10-35, and 1-40, some insight into the length and the sequence matching effects may be obtained.
authors.affiliation: Laboratory of Experimental and Computational Biology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA.
authors.forename: David
authors.initials: D
authors.lastname: Zanuy
authors.forename: Buyong
authors.initials: B
authors.lastname: Ma
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D003198:Computer Simulation; D004355:Drug Stability; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D058228:Islet Amyloid Polypeptide; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D046911:Macromolecular Substances; D009842:Oligopeptides; D021122:Protein Subunits; C478380:amylin (22-27)