In blue-light sensing using flavin (BLUF) domains, the side-chain orientation of key residues close to the flavin chromophore is still under debate. We report quantum refinements of the wild-type AppA BLUF protein from Rhodobacter sphaeroides starting from two published X-ray structures (1YRX and 2IYG) with different arrangements of the residues around the chromophore. Quantum refinement uses the same experimental X-ray raw data as conventional refinement, but includes data from quantum mechanics/molecular mechanics (QM/MM) calculations as restraints, which is expected to be more reliable than the normally employed MM data. In addition to quantum refinement, pure QM/MM geometry optimizations are performed for the 1YRX and 2IYG structures and for five models derived therefrom. Vertical excitation energies are computed at the QM(DFT/MRCI)/MM level to assess the resulting structures. The experimental absorption maximum of the dark state of wild-type AppA is well reproduced for structures that contain the Gln63 residue in 1YRX-type orientation. The computed excitation energies are red-shifted for structures with a flipped Gln63 residue in 2IYG-type orientation. The calculated 1YRX- and 2IYG-type hydrogen-bonding networks are discussed in detail, particularly with regard to the orientation of the chromophore and the Gln63, TrpI04, and Met106 residues.