We report the thermodynamics of binding Of D-galactose and deoxy derivatives thereof to the arabinose binding protein (ABP). The "intrinsic" (solute-solute) free energy of binding DeltaG(int)(0) at 308 K for the 1-, 2-, 3-, and 6-hydroxyl groups of galactose is remarkably constant (similar to-30 kJ/mol), despite the fact that each hydroxyl group subtends different numbers of hydrogen bonds in the complex. The substantially unfavorable enthalpy of binding (similar to30 W/mol) of 1-deoxygalactose, 2-deoxygalactose, and 3-deoxygalactose in comparison with galactose, cannot be readily accounted for by differences in solvation, suggesting that solute-solute hydrogen bonds are enthalpically significantly more favorable than solute-solvent hydrogen bonds. In contrast, the substantially higher affinity for 2-deoxygalactose in comparison with either 1-deoxygalactose or 3-deoxygalactose derives from differences in the solvation free energies of the free ligands.