TY - JOUR
T1 - Short peptide amyloid organization
T2 - Stabilities and conformations of the islet amyloid peptide NFGAIL
AU - Zanuy, David
AU - Ma, Buyong
AU - Nussinov, Ruth
N1 - Funding Information:
The research of R. Nussinov in Israel has been supported in part by the Magnet grant, by the Ministry of Science grant, and by the Center of Excellence in Geometric Computing and its Applications funded by the Israel Science Foundation (administered by the Israel Academy of Sciences), and by the Adams Brain Center. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract number NO1-CO-12400. The content of this publication does not necessarily reflect the view or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U.S. Government.
Funding Information:
We thank Drs. K. Gunasekaran, C.J. Tsai, and S. Kumar for discussions. In particular, we thank Dr. Jacob V. Maizel for encouragement. The computation times are provided by the National Cancer Institute's Frederick Advanced Biomedical Supercomputing Center and by the National Institutes of Health Biowulf.
PY - 2003/3/1
Y1 - 2003/3/1
N2 - 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 Aβ fragments 16-22, 24-36, 16-35, and 10-35, and the solid-state NMR data for Aβ fragments 16-22, 10-35, and 1-40, some insight into the length and the sequence matching effects may be obtained.
AB - 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 Aβ fragments 16-22, 24-36, 16-35, and 10-35, and the solid-state NMR data for Aβ fragments 16-22, 10-35, and 1-40, some insight into the length and the sequence matching effects may be obtained.
UR - http://www.scopus.com/inward/record.url?scp=0037339326&partnerID=8YFLogxK
U2 - 10.1016/S0006-3495(03)74996-0
DO - 10.1016/S0006-3495(03)74996-0
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AN - SCOPUS:0037339326
SN - 0006-3495
VL - 84
SP - 1884
EP - 1894
JO - Biophysical Journal
JF - Biophysical Journal
IS - 3
ER -