  Because human serum transferrin (hTF) exists freely in serum, it is a
potential target for cancer treatment drugs and in curing iron-overloaded
conditions in patients via long-term transfusion therapy. The understanding of
the interactions between hTF and metal ions is very important for biological,
pharmalogical, toxicological, and other protein engineering purposes. In this
paper, a simple linear free energy correlation is proposed to predict the
binding strength between hTF protein and metal cations. The stability constants
for a family of metal-hTF complexes can be correlated to the non-solvation
energies and the radii of cations. The binding strength is determined by both
the physical properties (charge and size or ionic radius) and chemical
properties (non-solvation energy) of a given cation. The binding strengths of
either divalent and trivalent metals can then be predicted systematically.
