Herein we describe an integrated approach — Molecular Sophe — for determination of the molecular structure of redox active cofactors in metalloproteins from an analysis of their high-resolution EPR spectra. Molecular Sophe involves the computer simulation of continuous-wave and orientation-selective pulsed EPR and electron nuclear double resonance (ENDOR) spectra. As aids to the correct analysis of these spectra, calculation of energy level diagrams, transition roadmaps, and transition surfaces can also be performed. This approach, based on molecular structure, promises to revolutionize the three-dimensional molecular (geometric and electronic) characterization of paramagnetic materials using a combination of high-resolution EPR spectroscopy and quantum chemistry calculations.