We are interested in the effect nearby amino acid side chains have on the pK_a of a water molecule bound to a Zn²⁺ ion in the enzyme carbonic anhydrase (CA). Our group previously showed that we could calculate reasonably well the pK_a in water of actual small molecules that mimic CA. We also showed that a small model of the enzyme that had a water molecule and three imidazole rings as Zn²⁺ ligands was much more acidic in less polar solvents because the acid form has a greater charge than the conjugate base. We now report our results for a larger model of CA that includes parts of five additional amino acids, two of which are negatively charged. In this model system, the conjugate base has a greater charge than the acid form. We obtained positions of the selected atoms from the 2CBA structure in the Protein Data Bank, added hydrogen atoms, performed a partial optimization using a 6-31+G(d) basis set and the B3LYP level of theory, obtained improved electronic energies using a 6-311++G(2d,2p) basis set, and calculated the energy of the aqua and hydroxy form in various solvents using the PCM continuum model.