Fluorescent Rhodopsins: A Challenging Test for Cost-Effective QM/MM Approaches

In this study, we evaluate the performance of two cost-effective models, namely, TD-DFT and ΔSCF methods, combined with different molecular mechanics models, to predict the photophysical and photochemical properties of a set of fluorescent mutants of the microbial rhodopsin Archaerhodopsin-3. We investigate absorption energies and excited-state isomerization barriers of the embedded retinal protonated Schiff-base chromophore by comparing different DFT functionals as well as different approximations of the embedding model. For absorption energies, CAM-B3LYP demonstrates the most consistent alignment with experiments among the functionals tested, whereas the embedding potentials exhibit similar accuracy. However, incorporating linear response corrections within the polarizable TD-DFT/MM framework enhances accuracy. The photoisomerization barriers, instead, exhibit a pronounced sensitivity to the choice of embedding model, underscoring the complex role that environmental factors play in modulating predictions of excited-state processes. For the two properties here investigated, ΔSCF/MM presents qualitatively similar behavior with respect to TD-DFT for all the tested embedding models.