Ionic liquids

as a kind of novel green solvents

have been widely applied to structural stability study of protein due to their unique physicochemical properties. In this study

insulin was chosen as a heat-sensitive protein medicine to research the structural stability of protein in various imidazolium ionic liquids from a molecular insight by using molecular dynamics simulation. The results indicate that the ionic liquids are able to stabilize the molecular structure of insulin effectively at room temperature compared with aqueous solution. The RMSD values and the secondary structure of insulin show that the weaker the hydrogen-bond basicity of anion is

the shorter the alkyl chain of cation is

the more stable the molecular structure of insulin is. In order to explain thoroughly the effect of alkyl chain length of ionic liquid on the stability of the protein

the interaction and the number of contact between the insulin and dicyanamide imidazolium ionic liquids with different alkyl chain length are further analyzed. It is found that the cation stabilize effectively the molecular structure of insulin which relies mainly on the electrostatic interaction between the insulin and the 1-methylimidazole of cation. Comparing to ionic liquids with long alkyl chain

the interaction between the insulin and ionic liquids is more powerful

and the insulin also adsorb more anion and 1-methylimidazole of cation in ionic liquids with short alkyl chain. All these results indicate that the ionic liquids with short chain alkyl indeed improve the molecular structural stability of insulin. Generally

the molecular dynamic simulation

as adopted to this research

provides a molecular insight to investigate the stability of insulin in ionic liquids

which is important and essential for molecular design of ionic liquids and stability study of heat-sensitive protein drugs.