To investigate whether RBFE-Space derivatives are sufficient placeholders to model statistical fluctuations of their drug-like counterparts RBFEs, 214 'original' perturbations (i.e. the perturbations from nine publicly available congeneric series) were simulated in quintuplicate for 1ns per λ window (n=11). Subsequently, all combinations of phases were compared (figure ). For perturbations that give large SEM values quintuplicates runs are insufficient to obtain consistent results for a given edge processed in two directions (A->B or B->A), which introduces noise in correlations of these quantities (figure , left-hand side). To remedy this, a logarithmic scale was adopted (figure , right-hand side) when comparing SEM (or any other type of variance) arrays, which squashes larger deviations with respect to smaller deviations. This is justified because our approach does not need to estimate accurately large SEM values since edges with large SEM values will be discarded during network generation.