The 2D_3D representation composed of all the chemoinformatic features supported by RDKit 16 consistently outperformed the physics-based representations (MDenerg, MDenerg_LR and PLEC) both in model accuracy and the rate at which strongly binding ligands were identified. The PLEC fingerprint representation was finding strong binders much slower than the others. Meanwhile, the 2D_3D representation yielded the same top ligands more consistently than other representations (Fig. ).