In summary, a general approach was disclosed to quantitatively relate enzyme and ligand features to experimental observables; specifically, enzyme and ligand structures from either IFD or aMD/MM were related to the observed enantioselectivity in a photoenzymatic radical cyclization using statistical models. The resultant statistical models were mechanistically insightful and provided new perspectives on the origin of enantioselectivity in GluER systems. Furthermore, the utility of the statistical modeling strategy was demonstrated by predicting the enantioselectivity for out-of-sample combinations of mutants and substrates, with a particular emphasis on substrate scope to complement contemporary predictive approaches. Future applications of this workflow will include enhancement of enzymatic descriptors and virtual screening of enzyme mutants for reaction engineering.