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.