• Molecular dynamics
• Multiscale methods
• Photobiology
• Protein structure
• Structural biology

The photochemistry and photophysics of organic chromophores in photoresponsive proteins can be tuned by non-covalent protein-chromophore interactions, which are experimentally difficult to access with a temporal resolution. Here, we have combined classical molecular dynamics simulations and multiscale QM/MM(pol) calculations to study light-harvesting antennae from purple bacteria (LH2) and synthetic flavin-based fluorescent proteins (FbFPs), derived from plant LOV (light, oxygen, and voltage) sensing domains, with improved fluorescence (iLOV). For the LH2 complexes, we found out that the mechanisms that govern their adaptation (and spectral tuning) to different light conditions exploit the different H-bonding environment around the bacteriochlorophyll pigments to dynamically control both internal and inter-pigment degrees of freedom. The results obtained for the FbFPs indicate that the H-bonding dynamics impact the excitation and emission vertical energies of the studied systems, but they cannot explain the increased fluorescence. Instead, such an improvement (increased fluorescence) is reached by a better packing of the flavin binding-site induced by specific mutations which stabilize the chromophore through optimized van der Waals interactions.