We performed an enhanced conformation sampling, multicanonical molecular dynamics simulation, of humanin in two solvents: pure water and 30% 2,2,2-trifluoroethanol (TFE)/water co-solvent. Computed helix content at 280 K was 4% in water and 25% in TFE/water. In both solvents, computed free-energy landscape consisted of clearly distinguishable clusters at 280 K. However, the cluster positions in the landscape had no overlap between the water and TFE/water systems. The clusters in TFE/water involved various types of helical structures. Preferential solvation by TFE was seen around the helical regions of humanin. Hydrophobic residues and TFE molecules worked together to induce the helix formation. (c) 2008 Elsevier B. V. All rights reserved.