Enzyme structure and function depend to some extent on enzyme net charge and charge location. Altering the charge of even a single residue may affect the interaction between enzyme and substrate such that all catalytic activity is lost. In this study we investigated the effect of net charge and charge location on the enzymatic activity of synthetic mutants of bacteriophage T4 lysozyme in the presence of colloidal silica. Enzymatic activity decreased upon adsorption, and these changes were variant-specific. Results were interpreted with reference to differences in adsorbed enzyme structure and orientation, and electrostatic effects. By exploring the effects of enzyme charge on adsorption, it may be possible to gain a better understanding of how enzyme structure influences adsorption and function at an interface.