Protein and peptide aggregation into amyloid plaques is associated with a large variety of neurodegenerative diseases. The definition of the molecular bases of these pathologies is hampered by the transient nature of pre-fibrillar small-oligomers that are considered the toxic species. The ability of the peptide GNNQQNY to form amyloid-like structures makes it a good model to investigate the complex processes involved into amyloid fiber formation. By employing full atomistic replica exchange molecular dynamics simulations, we constructed the free energy Surface of small assemblies of GNNQQNY to gain novel insights into the fiber formation process. The calculations suggest that the peptide exhibits a remarkable tendency to form both Parallel and antiparallel beta-sheets. The data show that GNNQQNY preference for parallel or antiparallel beta-sheets is governed by a subtle balance of factors including assemblies' size, sidechain-sidechain interactions and pH. The samplings analysis provides a rationale to the observed trends. (C) 2008 Elsevier Inc. All rights reserved.