Fibril aggregation inhibitory activity of the beta-sheet breaker peptides: a molecular docking approach.
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.
Chini
Maria Giovanna
MG
Department of Pharmaceutical Sciences, University of Salerno, Fisciano (SA), Italy.
Scrima
Mario
M
D'Ursi
Anna Maria
AM
Bifulco
Giuseppe
G
D016229:Amyloid beta-Peptides / Q000737:chemistry; D003198:Computer Simulation; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010455:Peptides; C075222:amyloid beta-protein (1-42)