Chemical reactivity of 2HIU insulin using the Fukui Function

In the present work we have analyzed the chemical reactivity of 10 experimental conformers reported for human insulin 2HIU. Through the semiempirical PM6 method, descriptors of reactivity derived from the functional density theory were calculated, such as ionization energy, hardness, electrophilicity and frontier orbitals. Additionally, insulin 2HIU was optimized through the MOZYME linear scaling method and the level of theory ONIOM method (B3LYP/6-311++G(2p,2d)//UFF). The results obtained indicate that the geometry in the region of the cysteines CYS7A-CYS7B is similar to that predicted by the semiempirical method PM6 and the level of theory ONIOM(B3LYP/6-311++G(2p,2d)//UFF). Only the conformer 6 reported by Hue et al showed activity in the cysteine region, a position that has been experimentally identified with the biological activity of insulin. The results obtained suggest that a change in conformation of 2HIU drastically changes the reactivity of insulin and may inhibit its biological activity.