The zeta, or electrokinetic, potential is the effective charge energy of a molecule in a solution, defining its electrostatic interactions in the solution. A computational protocol for computing zeta potential from the high-resolution structures of proteins (ZPRED) is described. This model considers both protein and solution components and incorporates a number of electrokinetic models that account for many of the complexities of protein electrophoresis. Experimental observations of electrophoretic mobilities using a benchtop light scattering instrument match computed mobilities for different proteins over a wide range of aqueous solution conditions. ZPRED is a tool for optimizing protein sequence and solution conditions (pH, ionic composition and strength, temperature) to disperse molecules by charge repulsion, preventing aggregation. This is an important factor in enhancing the stability of engineered biologics or industrial protein catalysts.