Statistical analysis. Seven of the eight variables were evaluated to find statistically significant differences between the ensembles generated by the tested software, and to evaluate reproducibility in the non-deterministic algorithms (Torsional diffusion and Moltiverse). Unless otherwise stated, statistical analysis was carried out on the aggregated values of the different molecules and replicas for each tested algorithm/mode (Table ). For RMSDlow and RMSDhigh, all values at and below the 2.5th and at and above the 97.5th percentiles, respectively, instead of the mean value were considered for this purpose. To assess reproducibility, the conformer ensembles of the independent replicas for Torsional Diffusion and Moltiverse were compared by the RMSDmin metric for each molecule. Statistical analysis was conducted using the R software version 4.3.2 . The data were first assessed for normality and homogeneity of variances . Based on these assessments a Generalized Linear Model (GLM) with Gamma distribution using identity as the link function was employed for every variable. To evaluate the effect of the factors on the data behavior was performed ANOVA in every GLM by type II sum of squares, and according to the results, multiple comparisons were performed using a post hoc analysis with the Tukey