Forster resonance energy transfer (FRET) to reactions involving ligands and aromatic amino acids can substantially impact the fluorescence properties of a protein ligand complex, an impact intimately related to the corresponding binding mode. Structural characterization of such binding events in terms of intermolecular distances can be done through the well-known R-6 distance-dependent Forster rate expression. However, such an interpretation suffers from uncertainties underlying Forster theory in the description of the electronic coupling that promotes FRET, mostly related to the dipole dipole orientation factor, dielectric screening effects, and deviations from the ideal dipole approximation. Here, we investigate how Forster approximations impact the prediction of energy transfer dynamics in the complex between flurbiprofen (FBP) and human serum albumin (HSA), as well as a model FBP-Trp dyad, in which recent observation of enantioselective fluorescence quenching has been ascribed to energy transfer from FBP to Trp. To this end, we combine classical molecular dynamics simulations with polarizable quantum mechanics/molecular mechanics calculations that allow overcoming Forster approximations. On the basis of our results, we discuss the potential of structure-based simulations in the characterization of drug-binding events through fluorescence techniques. Overall, we find an excellent agreement between theory and experiment both in terms of enantioselectivity and FRET times, thus strongly supporting the reliability of the binding modes proposed for the (5) and (R) enantiomers of FBP. In particular, we show that the dynamic quenching arises from a small fraction of drug bound to the secondary site of HSA at the interface between subdomains IIA and IIB, whereas the enantioselectivity arises from the larger flexibility of the (S)-FBP enantiomer in the binding pocket.