Structures of a peptide fragment Of β2-microglobulin studied by replica-exchange molecular dynamics simulations -: Towards the understanding of the mechanism of amyloid formation

We investigate in detail the structural properties of the monomeric peptide fragment that corresponds to residues 21-31 of beta(2)-microglobulin. As a first step towards the understanding of the mechanism of the amyloid formation, we have performed a replica-exchange molecular dynamics simulation of this peptide with explicit water molecules. We analyze various structural properties as functions of temperature. Although the corresponding part of the native protein is a fully extended beta-strand, our results show that beta-hairpin structures are formed with high frequency around 310 K. We conjecture that this beta-hairpin formation is closely related to the amyloid fibrillogenesis. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.