title: Fibril aggregation inhibitory activity of the beta-sheet breaker peptides: a molecular docking approach.
abstract: In the present study, we used a molecular docking as a rapid, interactive method to study the inhibition of fibrillogenesis process by beta-sheet breaker peptide (BSB) (Ac-L(1)-V(2)-(NMet)F(3)-F(4)-A(5)-NH(2)). Our aim was to find the complex (Abeta:BSB) that blocks the aggregation of the fibrils, and to identify the binding sequences for the small peptides on Abeta(1-42). An NMR structure solved by Lührs et al. in 2005 was used to study the interaction of BSB with the amyloid aggregated forms. From our preliminary step-by-step docking studies, the L(17)-D(23) sequence seems to be one of the most common active sites of Abeta(1-42), and critical in amyloid fibril formation. We note that a single molecule of BSB does not influence the interaction between the two fibrils, while a little excess of BSB (two molecules) with respect to the amyloid does not completely block but undoubtedly obstructs the aggregation process.
authors.affiliation: Department of Pharmaceutical Sciences, University of Salerno, Fisciano (SA), Italy.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Chini
authors.forename: Mario
authors.initials: M
authors.lastname: Scrima
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: D'Ursi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bifulco
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry; D003198:Computer Simulation; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010455:Peptides; C075222:amyloid beta-protein (1-42)