Two phenomena reduce the electrostatic repulsion between protein molecules in solution: charge heterogeneity (patchiness) and charge fluctuation. In this work, the electrostatic interaction energy for two protein molecules is computed as a function of separation and orientation. The results are based on solutions of the linearized Poisson-Boltzmann equation for an arbitrary prescribed surface charge distribution. A boundary element technique yields a numerical solution for the electrostatic potential on the protein surface that is then used to compute the reversible charging work. The results indicate that the two mechanisms act in a complementary fashion. Correlations in charge fluctuations reduce the net charge on the molecules and produce a long-range effect, while charge patchiness becomes significant at separations smaller than the Debye length. Both effects are included in a DLVO-type interaction potential that is used to match published second virial coefficients of lysozyme. Compared to earlier studies, the best-fit values of the effective Hamaker constant are much less sensitive to ionic strength and in better agreement with estimates based on Lifshitz theory.