Large, well-ordered crystals are required for X-ray diffraction studies of proteins, but it is often difficult to obtain suitable crystals. Proteins frequently precipitate as amorphous solids or form crystals that are too small. Larger crystals often lack order, which may reflect a nonspecific character in the protein-crystal interaction. To investigate the assembly process, we studied colloidal interaction forces between a protein crystal and a molecule in solution. Three factors control the interaction potential : the protein charge distribution, the charge on the crystal, and the effective Hamaker constant for the dispersion force. The relative strengths of electrostatic and dispersion forces were determined for a range of surface charges and Hamaker constants for a model protein, lysozyme. We found that the balance between electrostatic repulsion and van der Waals attraction is delicate. The free energy surface of the protein-crystal interaction shows many shallow minima, which is consistent with the protein’s ability to crystallize in different forms. Charge heterogeneity on the crystal surface and the molecule is important in the nucleation of new crystal layers and in the migration of molecules across the surface to growth sites. The Boltzmann-weighted interaction potential of the molecule differs strongly from that of a uniformly charged sphere when the crystal surface is highly charged.