Group additive contributions to the alcohol-induced α-helix formation of melittin: implication for the mechanism of the alcohol effects on proteins

Abstract

Detailed analysis of the effects of alcohols on proteins and peptides is important because of its wide range of applications in many fields. Whereas melittin, a major component of honeybee venom, is unfolded in an aqueous environment, the addition of alcohols induces an α-helical structure. We used circular dichroism (CD) to compare the effects of various alcohols on melittin. Whereas the α-helical state was basically independent of alcohol species, the effectiveness of alcohols varied significantly. Among alkanols, the effectiveness was proportional to the bulkiness of hydrocarbon groups, indicating that the hydrocarbon group contributes positively to the alcohol effects. Comparison of alcohols with the same hydrocarbon group but a different number of hydroxyl groups showed that the hydroxyl groups contribute negatively to the alcohol effects. Comparison of several halogenols indicated that halogen increases the effectiveness in the order of F < C l< Br. These results suggested that the effects of alcohol can be interpreted by the additive contributions of each of the constituent groups of the alcohol, which are proportional to the solvent-accessible surface area. However, for markedly effective alcohols such as 1,1,1,3,3,3-hexafluoro-2-propanol, the aggregation of alcohols was suggested to further enhance these effects. We have constructed equations for estimating the effectiveness of alcohols in inducing α-helical structure, which should also be useful for predicting the other effects of alcohols on proteins.