Thomas-Otavio Peulen, Daria Maksutova, Thorben Cordes
Fluorescence spectroscopy and modeling provide powerful means to characterize biomacromolecular structures, dynamics, and interactions. Förster resonance energy transfer serves as a key technique for this because of its nanometer scale distance sensitivity. Quantitative interpretation of fluorescence data relies on models that link molecular structure to observable spectroscopic quantities and vice versa. Integrative modeling frameworks combine fluorescence observables with complementary structural information to infer molecular structures and conformational ensembles. This review outlines conceptual components of fluorescence-based modeling, discusses dye representations, and highlights advances toward refined models enabling quantitative structural analysis. Finally, we discuss the prediction of spectroscopic properties of dyes based on biomolecular structures and fluorescence assay design beyond traditional Förster resonance energy transfer applications.