Cargando…

Peptide ligand screening of α-synuclein aggregation modulators by in silico panning

BACKGROUND: α-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 α-synuclein cytotoxicity, and an aggregation accelerator has recently been reported to reduce α-synuclein cy...

Descripción completa

Detalles Bibliográficos
Autores principales: Abe, Koichi, Kobayashi, Natsuki, Sode, Koji, Ikebukuro, Kazunori
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2244645/
https://www.ncbi.nlm.nih.gov/pubmed/18005454
http://dx.doi.org/10.1186/1471-2105-8-451
Descripción
Sumario:BACKGROUND: α-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 α-synuclein cytotoxicity, and an aggregation accelerator has recently been reported to reduce α-synuclein cytotoxicity. Therefore, amyloid aggregation modulating ligands are expected to serve as therapeutic medicines. RESULTS: We screened peptide ligands against α-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 α-synuclein. CONCLUSION: We demonstrated that it is possible to screen α-synuclein-binding peptides by in silico panning. The screened peptides bind to α-synuclein, thus affecting the aggregation of α-synuclein.