Simulation studies on the stabilities of aggregates formed by fibril-forming segments of alpha-Synuclein.
We performed molecular dynamics simulations for various oligomers with different beta-sheet conformations consisting of alpha-Synuclein 71-82 residues using an all atom force field and explicit water model. Tetramers of antiparallel beta-sheet are shown to be stable, whereas parallel sheets are highly unstable due to the repulsive interactions between bulky and polar side chains as well as the weaker backbone hydrogen bonds. We also investigated the stabilities of double antiparallel beta-sheets stacked with asymmetric and symmetric geometries. Our results show that this 12 amino acid residue peptide can form stable beta-sheet conformers at 320K and higher temperatures. The backbone hydrogen bonds in beta-sheet and the steric packing between hydrophobic side chains between beta-sheets are shown to give conformational stabilities.
School of Chemistry, Seoul National University, Seoul, Korea.
Jeseong
J
Yoon
Soonmin
S
Jang
Kyunghee
K
Lee
Seokmin
S
Shin
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism
D000682:Amyloid; D010446:Peptide Fragments; D051844:alpha-Synuclein