In this paper, protein surface interaction maps were generated by performing coarse-grained protein surface calculations. This approach allowed for the rapid determination of the protein surface interaction energies at a range of orientations and distances. Interaction maps of lysozyme indicated that there was a contiguous series of orientations corresponding to several adjacent preferred binding regions on the protein surface. Examination of these orientations provided insight into the residues involved in suface interactions, which qualitatively agreed with the retention data for single-site mutants. Interaction maps of lysozyme single-site mutants were also generated and provided significant insight into why these variants exhibited significant differences in their chromatographic behavior. This approach was also employed to study the binding behavior of CspB and related mutants. The results indicated that, in addition to describing general trends in the data, these maps provided significant insight into retention data of the single-site mutants. In particular, subtle retention trends observed with the K12 and K13 mutants were well-described using this interaction map approach. Finally, the number of interaction points with energies stronger than -2 kcal/mol was shown to be able to semi-quantiatively predict the behavior of most of the mutants. This rapid approach for calculating protein-surface interaction maps is expected to facilitate future method development for separating closely related protein variants in ion-exchange systems.