Quality and structural diversity measures. Eight descriptors were calculated to evaluate the conformational diversity of the ensembles and the ability of the algorithms to reproduce the experimental conformations. For every experimental structure collected in the dataset of a given molecule, the best-fit RMSD was computed against all conformers generated by an algorithm and the minimum RMSD value (RMSDmin) was selected as measure of the accuracy of reproducing ). Additionally, the mean of the RMSDmin values at and below the 2.5th percentile (RMSDlow) and the mean of the RMSDmin values at and above the 97.5th percentile (RMSDhigh) were calculated as well to obtain an estimate of the lower and upper bounds of the prediction accuracy, respectively. The precision of an algorithm to reproduce experimental structures was defined as the standard deviation of the RMSDmin values (RMSDstd). Conformational diversity was assessed using two complementary approaches: (i) the RDGYR of all the generated conformers by each algorithm, and (ii) the RMSD between the generated conformers. The range of the RDGYR (RDGYRrange), calculated as the difference between the mean of the RDGYR values at and below the 2.5th percentile and the mean of the RDGYR values at and above the 97.5th percentile values of the generated conformers, determines whether an algorithm can generate compact, extended, or both types of conformations across all the studied molecules. For the RDGYRrange, a higher value indicates a greater molecular stretching.