Abstract: Methods and systems are provided for simulating metabolic interactions between a microbiome and a chemical compound. In one embodiment, a method includes predicting, with a trained deep neural network, a plurality of enzymes potentially responsible for metabolism of a chemical compound, generating a three-dimensional individual-specific model of a microbiome including one or more microorganisms associated with the plurality of enzymes, and simulating, with the three-dimensional individual-specific model, metabolism of the chemical compound in the microbiome over time. In this way, the individual-specific metabolism of chemical compounds, such as drug compounds, in microbiomes, such as human gut microbiomes, may be reliably predicted in a high-throughput fashion while accounting for three-dimensional compound structure.