A computational protocol to probe the role of solvation effects on the reduction potential of azurin mutants

Semiquantitative relationships between thermodynamic parameters of Cu2+ reduction experimentally measured for a series of azurin mutants and the solvation free energy of the oxidized state of the proteins were derived. Solvation free energy calculations were carried out within an ONIOM/PCM scheme specifically adapted to this protein series. The method proved to be able to capture the main determinants of the measured reduction parameters, providing satisfactory predictions of the E degrees '.