Aggregation of Islet amyloid polypeptide ( IAPP) is believed to play a critical role in the pathogenesis of Type II Diabetes Mellitus. In an attempt to gain details on the early events of this process, here we performed MD simulations of the spontaneous assembly of three replicas of human IAPP. Systems containing the Cys2-Cys7 disulfide bridge exhibited a greater stability and a decreased tendency to evolve into beta-sheet rich structures if compared to the disulfide-depleted variants. Conversely, the stability of assemblies constituted by the rat isoforms was shown to be independent from the presence of the disulfide bridge. (C) 2008 Elsevier B.V. All rights reserved.