Fibril aggregation inhibitory activity of the β-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)-NH2)- Our aim was to find the complex (A beta:BSB) that blocks the aggregation of the fibrils, and to identify the binding sequences for the small peptides on A beta(1-42). An NIVIR structure solved by Luhrs et at. 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 A beta(1-42), and critical In amylold 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. Copyright (C) 2008 European Peptide Society and John Wiley & Sons, Ltd.