Chemical reactivity of 2HIU insulin using the Fukui Function

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