The results for each RMSD cutoff are shown in Figure . The larger the RMSD threshold was set to, the more conformer pairs were considered the same, leading to a decrease in the number of false positives (FP) and true negatives (TN) along with an increase in the number of true positives (TP) and false negatives (FN). This leads directly to the observed overall trend of positive predictive value (PPV, Eq. 6) steadily increasing and negative predictive value (NPV, Eq. 7) steadily decreasing in all three categories. To achieve the best agreement between TABS and RMSD, both the PPV and NPV values should be maximized. This leads us to choose the RMSD threshold for each category at the point where the curves for PPV and NPV cross. The intersection point moves towards larger RMSD threshold values from low to high flexibility, a finding that is in line with the well-known size dependence of RMSD thresholds .