NBO partial charges at ten key atoms were gathered from the ground state structure of each reduced cofactor. Additionally, nucleophilic and electrophilic condensed Fukui indices were calculated using NBO partial charges for each after the subtraction and addition of an electron, respectively (Figure , Step IV). Predictive modeling was done using ROBERT software version 1.0.6 (Figure , Step V). Our final model was trained using DFT-level descriptors after testing numerous model architectures (Figure ) before settling on the highest-performing one, a multivariate linear regression model with a 101:18:13 train:validation:test split. Default settings were used except permutation feature importance analysis (PFI). PFI scores were calculated in ROBERT and tabulated, then used to isolate the 8 most important descriptors to train the model. More details about the use of ROBERT software for predictive modeling can be found in section 7 of the supplemental information.