Computational studies on the binding of β-sheet breaker (BSB) peptides on amyloid βA(1-42)

Alzheimer's disease starts with the aggregation of beta -amyloid peptides overproduced in the brain. The pathognomic plaques contain 50-100 peptides in parallel and/or antiparallel beta -pleated sheet structure. Short peptide fragments called beta -sheet breaker (BSB) peptides can bind specifically to beta -amyloid peptides hindering the association and aggregation, The 3D structures of the molecular associates between betaA(6-34) and BSB peptides (Soto's LPFFD, Tjernberg's KLVFF and two new ones) were calculated theoretically by AMBER force field based docking algorithms. The calculated structures emphasize the directing effect and pivotal role of electrostatic forces and the importance of the hydrophobic interactions of the side-chains in binding of BSB peptides to the beta -amyloid peptide. (C) 2001 Elsevier Science B.V. All rights reserved.