Thermodynamics of the interaction between Ni2+ and human growth hormone (hGH) were determined at 27 degrees C in Nail solution by isothermal titration calorimetry. A new method to predict protein penetration and the effect of metal ions on the stability of proteins is introduced. The new solvation model was used to reproduce the enthalpies of Ni2+-hGH interaction over the whole range of Ni2+ concentrations. The solvation parameters recovered from the new equation, attributed to the structural change of hGH and its biological activity. (C) 2006 Elsevier B.V. All rights reserved.