In this study, we assess the validity of SF-TDDFTB to study the photoisomerisation reactions of a retinal protonated Schiff base, an oxindole photoswitch, a protonated green fluorescent protein chromophore and a photodrug named phototrexate (see chemical structures in Figure ). For this purpose, we compare the potential energy surface of S 0 and S 1 states of SF-TDDFTB compared to all-electron SF-TDDFT and MRSF-TDDFT, which has been shown to be an accurate method for describing the excited states of large molecular systems.