A single charge screening model of surface charge sensors in liquids (De Vico et al., Nanoscale, 2011, 3, 706–717) is extended to multiple charges to model the effect of the charge distributions of analyte proteins on FET sensor response. With this model we show that counter-intuitive signal changes (e.g. a positive signal change due to a net positive protein binding to a p-type conductor) can occur for certain combinations of charge distributions and Debye lengths. The new method is applied to interpret published experimental data on Streptavidin (Ishikawa et al., ACS Nano, 2009, 3, 3969–3976) and Nucleocapsid protein (Ishikawa et al., ACS Nano, 2009, 3, 1219–1224).