It can be useful to describe the Gibbs free energy changes for the binding to a protein of a molecule, A-B, and of its component parts, A and B, in terms of the "intrinsic binding energies" of A and B, DeltaG(A) (i) and DeltaG(B) (i), and a "connection Gibbs energy," DeltaG(s) that is derived largely from changes in translational and rotational entropy. This empirical approach avoids the difficult or insoluble problem of interpreting observed DeltaH and TDeltaS values for aqueous solutions. The DeltaG(i) and DeltaG(s) terms can be large for binding to enzymes and other proteins.