A hybrid molecular dynamics/continuum electrostatics method is proposed for free energy calculations that involve the creation or deletion of net charges in a solvated macromolecule, which extends and simplifies an earlier method. A limited, spherical region of interest is treated microscopically; the remainder of the system is treated as a heterogeneous dielectric continuum. The spherical region contains part of the macromolecule and a limited number of explicit solvent molecules, while the outer region contains the remainder of the macromolecule and bulk solvent. In a first step, the dielectric constant of the macromolecule in the outer region is changed from a value typical of the macromolecule (similar to 1-4 for a protein) to a value typical of a bulk solvent. Second, the mutation is introduced with a molecular dynamics simulation for the spherical region, including the reaction field due to the now-homogeneous outer region, for which analytical expressions are available. Third, the outer macromolecular dielectric constant is changed back to its original value. The free energies for steps one and three are obtained from continuum electrostatics. The method is used to calculate the free energy to mutate a negatively charged aspartate ligand into a neutral asparagine in the active site of aspartyl-tRNA synthetase and shown through comparison to the earlier method to be efficient and accurate.