The computational expense of QFVina and QFVinardo is greater than that of traditional flexible ligand Vina and Vinardo docking, but not prohibitively so. QFVina and QFVinardo perform docking by looping over all stored conformations of a given ligand. For flexible ligands, the number of conformations is typically a few dozen, and we retained up to 100 conformations during the construction of the QM conformational databases. In contrast, traditional Vina and Vinardo perform a single flexible docking procedure with the same ligand, but flexible docking is inherently slower than the rigid body docking used by QFVina and QFVinardo.