Isothermal titration calorimetry (ITC) is a powerful and highly sensitive technique commonly used to study interactions between biomolecules in dilute aqueous solutions, both from thermodynamic and kinetics points of view. In this report, we show that ITC may be used to follow the binding of ligands such as amino acids to the surface of inorganic materials such as gold nanoparticles. More specifically, we have studied the binding of one basic amino acid, lysine, and an acidic amino acid, aspartic acid, with aqueous gold nanoparticles at physiological pH. Strong binding of aspartic acid with the gold nanoparticles under these conditions is indicated by ITC, while weak binding was observed in the case of lysine. The differences in binding are attributed to protonation of amine groups in lysine at physiological pH (pI ∼ 9.4) while they are not protonated for aspartic acid (pI ∼ 2.77). That this is the likely mechanism is indicated by the ITC measurement of binding of lysine with nanogold at pH 11 (when the amine groups are not protonated). The binding of the amino acids with gold nanoparticles has been validated with other techniques such as gel electrophoresis and X-ray photoemission spectroscopy.