A DFT study on the microscopic ionization of cysteine in water

The molecular equilibria involved in the second and third macroscopic deprotonation processes of Cys have been theoretically characterized at B3LYP/6-31++G** computing level. The role of solvent was analyzed by using the supermolecule (up to six discrete water molecules), the continuum, and the hybrid supermolecule-continuum models. Also, a novel approach to reveal the solvation effect of the bulk water was employed. Calculations performed with the supermolecule or the Onsager models overestimate absolute pKas, whereas the PCM continuum model yields data much closer to the experimental values. The supermolecule-PCM approach estimates the pKa values for the amino group much better than for the thiol group.