In the second method, VBur is first calculated for the total probe ensemble using Morfeus. To accomplish this, the ensemble is enclosed within a large sphere and the percentage of sphere volume occupied by the conformers is computed (Figure ). This method is significantly slower than the first (Table ), but is implemented for ensemble, as an interpretable method to parametrize the shape of the cavity by the maximum (B5) and minimum (B1) widths perpendicular to the structure binding axis (L) (Figure ).