Therefore, to reflect both enzyme promiscuity and specificity, 1-10 times as many corresponding unlabeled (considered as negative) enzyme-substrate pairs were included in the dataset. . Schematic of the computational methodology used for exploring the binding mode between substrates and enzymes. First, five putative binding sites were used for docking calculations. Second, the top-ranked docking poses were refined by all-atom molecular dynamics simulations. Finally, the binding poses were re-ranked using molecular mechanics-generalized Born and surface area (MM-GBSA)-calculated binding free energies. The most probable binding pose was selected for binding mode analyses.