Paper Citing NAMD - Abstract
Raman, E. Prabhu; Takeda, Takako; Barsegov, Valer; Klimov, Dmitri K.
Mechanical unbinding of A beta peptides from amyloid fibrils
JOURNAL OF MOLECULAR BIOLOGY, 373:785-800, OCT 26 2007
Using the experimental structures of A amyloid fibrils and all-atom molecular dynamics, we study the force-induced unbinding of A beta peptides from the fibril. We show that the mechanical dissociation of A beta peptides is highly anisotropic and proceeds via different pathways when force is applied in parallel or perpendicular direction with respect to the fibril axis. The threshold forces associated with lateral unbinding of A peptides exceed those observed during the mechanical dissociation along the fibril axis. In addition, A fibrils are found to be brittle in the lateral direction of unbinding and soft along the fibril axis. Lateral mechanical unbinding and the unbinding along the fibril axis load different types of fibril interactions. Lateral unbinding is primarily determined by the cooperative rupture of fibril backbone hydrogen bonds. The unbinding along the fibril axis largely depends on the interpeptide Lys-Asp electrostatic contacts and the hydrophobic interactions formed by the A beta C terminal. Due to universality of the amyloid structure, the anisotropic mechanical dissociation observed for A fibrils is likely to be applicable to other amyloid assemblies. The estimates of equilibrium forces required to dissociate A beta peptide from the amyloid fibril suggest that these supramolecular structures are mechanically stronger than most protein domains. (c) 2007 Elsevier Ltd. All rights reserved.
