Influence of preformed Asp23-Lys28 salt bridge on the conformational fluctuations of monomers and dimers of Abeta peptides with implications for rates of fibril formation.

ABSTRACT: Recent experiments have shown that the congener Abeta(1-40)[D23-K28], in which the side chains of charged residues Asp23 and Lys28 are linked by a lactam bridge, forms amyloid fibrils that are structurally similar to the wild type (WT) Abeta peptide, but at a rate that is nearly 1000 times faster. We used all atom molecular dynamics simulations in explicit water, and two force fields, of the WT dimer, a monomer with the lactam bridge (Abeta(10-35)-lactam[D23-K28]), and the monomer and dimers with harmonically constrained D23-K28 salt bridge (Abeta(10-35)[D23-K28]) to understand the origin of the enhanced fibril rate formation. The simulations show that the assembly competent fibril-like monomer (N*) structure, which is present among the conformations sampled by the isolated monomer, with s

SUBMITTER: Reddy G 

PROVIDER: S-EPMC3098509 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature