The additional conformational sampling was done to estimate the error associated with incomplete sampling by calculating the average reduction in E a for the top 100 and bottom 100 samples (Fig. ). For example, if the additional conformations merely rediscovered the same TS or higher energy TSs, then the reduction would be zero, but if they led to the discovery of lower barrier TSs, then the reduction would be positive. This experiment revealed that incomplete conformational sampling disproportionately affects the poorly predicted samples, with the most and least accurate populations showing mean E a reductions of ∼2.5 kcal/mol and ∼6.5 kcal/mol, respectively. The reaction with the largest E a reduction of ∼30 kcal/mol occurs in the poorly predicted samples versus a maximum reduction of ∼13 kcal/mol in the top 100 predictions (See Fig. for other relevant analyses). For the bottom 100 predictions that were intended after the IRC calculation (i.e., the 27 reactions where unintended TSs are not a confounding factor as revealed by the analysis in the next paragraph) the G→BEP model underestimates E a by 21.8 kcal/mol on average compared with a negligible mean signed error on the whole dataset (Fig. ), meaning that the model recognizes these reactions as being conformationally undersampled. The E a reduction of ∼2.5 kcal/mol observed in the best predictions can be considered a lower bound on the irreducible error of RGD1, assuming no other factors contribute to the error and that unintended reactions can be perfectly filtered. Thus while conformational sampling errors significantly contribute to the irreducible error for G2Ea prediction on RGD1, alone they cannot explain the majority of outliers that comprise the worst predictions.