A theoretical method is proposed to circumvent the orbital relaxation problem (variations in the orbital composition when the electron number in the system changes) in the analysis of the calculated electronic structure of a redox-active molecule. The method is based on a convenient partition of the electron-transfer integral: one contribution depends on the coupling of the molecule with the external redox partner; the other is an intrinsic feature of the molecule under study and takes into account the orbital relaxation upon reduction/oxidation. The method is applied to the electronic structure analysis of the active site of the electron-transfer protein azurin. (C) 2004 Elsevier B.V. All rights reserved.