The effects of alcohols on local protein structure have been simulated using computational approaches and model peptides. Molecular simulations were carried out on a 7-residue peptide created in both an extended conformation and an β£-helix to explore alcohol-induced changes in peptide structure. It was assumed that alcohols hydrogen bond at peptide carbonyl groups with an optimum geometry and compete with water molecules at these sites. Energy minimization of the peptide/alcohol assemblies revealed that alcohols induced a twist in the peptide backbone as a function of (1) the methylene chain length, (2) the hydrogen-bond geometry, (3) halogenation of the molecule, (4) concentration, and ( ) the dielectric constant. The rank ordering of the potencies of the alcohols was hexafluoroisopropanol ΟΎ trifluoroethanol Ο· pentanol ΟΎ butanol ΟΎ ethanol ΟΎ methanol. Helix destabilization by cosolvent was measured by examining the hydrogen-bond lengths in peptide structures that resulted from a combination of energy minimization and molecular dynamics simulations. Destabilization was also found to be dependent upon the chemical nature of the alcohol and the hydrogen-bond geometry. The data suggest that alcohols at low concentrations affect protein structure mainly through a combination of hydrogen-bonding and hydrophobic interactions that are influenced by the properties of the solvent.