title: Peptide ligand screening of alpha-synuclein aggregation modulators by in silico panning.
abstract: BACKGROUND
  alpha-Synuclein is a Parkinson's-disease-related protein. It forms aggregates in vivo, and these aggregates cause cell cytotoxicity. Aggregation inhibitors are expected to reduce alpha-synuclein cytotoxicity, and an aggregation accelerator has recently been reported to reduce alpha-synuclein cytotoxicity. Therefore, amyloid aggregation modulating ligands are expected to serve as therapeutic medicines.
  
  
  RESULTS
  We screened peptide ligands against alpha-synuclein by in silico panning, a method which we have proposed previously. In this study, we selected as the target a very hydrophobic region known as the amyloid-core-forming region. Since this region cannot be dissolved in water, it is difficult to carry out the in vitro screening of its peptide ligand. We carried out 6 rounds of in silico panning using a genetic algorithm and a docking simulation. After the in silico panning, we evaluated the top peptides screened in silico by in vitro assay. These peptides were capable of binding to alpha-synuclein.
  
  
  CONCLUSIONS
  We demonstrated that it is possible to screen alpha-synuclein-binding peptides by in silico panning. The screened peptides bind to alpha-synuclein, thus affecting the aggregation of alpha-synuclein.
authors.affiliation: Department of Biotechnology, Tokyo University of Agriculture and Technology, 2-24-13 Naka-cho, Koganei-shi, Tokyo, 184-8588, Japan. 50007831201@st.tuat.ac.jp
authors.forename: Koichi
authors.initials: K
authors.lastname: Abe
authors.forename: Natsuki
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Koji
authors.initials: K
authors.lastname: Sode
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ikebukuro
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D019281:Dimerization; D015195:Drug Design; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000648:ultrastructure; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D020539:Sequence Analysis, Protein / Q000379:methods*
chemical_list: D008024:Ligands; D046912:Multiprotein Complexes; D010455:Peptides