Aggregation of small peptides studied by molecular dynamics simulations

Dagmar Flöck ^{1 *}, Giulia Rossetti ¹, Isabella Daidone ², Andrea Amadei ³, Alfredo Di Nola ¹

¹Department of Chemistry, University of Rome La Sapienza, Rome 00185, Italy
²Computational Molecular Biophysics Group, IWR, University of Heidelberg, 69120 Heidelberg, Germany
³Department of Chemical Science, University of Rome Tor Vergata, Rome 00133, Italy

email: Dagmar Flöck (floeck@caspur.it)

Keywords

conformational changes � peptide aggregation � human calcitonin � human islet amyloid polypeptide

Abstract

Peptides and proteins tend to aggregate under appropriate conditions. The amyloid fibrils that are ubiquitously found among these structures are associated with major human diseases like Alzheimer's disease, type II diabetes, and various prion diseases. Lately, it has been observed that even very short peptides like tetra and pentapeptides can form ordered amyloid structures. Here, we present aggregation studies of three such small polypeptide systems, namely, the two amyloidogenic peptides DFNKF and FF, and a control (nonamyloidogenic) one, the AGAIL. The respective aggregation process is studied by all-atom Molecular Dynamics simulations, which allow to shed light on the fine details of the association and aggregation process. Our analysis suggests that naturally aggregating systems exhibit significantly diverse overall cluster shape properties and specific intermolecular interactions. Additional analysis was also performed on the previously studied NFGAIL system. Proteins 2006. © 2006 Wiley-Liss, Inc.