Phase I enzymes, which are responsible for the metabolism of more than 90% of FDA approved drugs, catalyze highly diverse types of reactions and produce metabolites with substantial structural variability. We propose a system for simultaneously labeling sites of metabolism and reaction types, classifying them into five key reaction classes: stable and unstable oxidations, dehydrogenation, hydrolysis, and reduction. These classes unambiguously identify 21 types of phase I reactions, which cover 92.3% of known reactions in our database. We used this labeling system to train a neural network on 20,736 human phase I metabolic reactions, able to identify reaction-type specific sites of metabolism with a cross-validated accuracy of 97.1% area under the receiver operator curve.
Please cite: