Balloon employed a multiobjective genetic algorithm for generating ensembles of molecular conformers. The number of generated conformations was determined by the 'nconfs' switch, which was set to 1000, and the convergence criterion based on the gradient root-mean-square (rms) was set to 0.1 kcal mol -1 Å -1 . Balloon conducts conformation generation, RMSD checks, and eliminates similar conformations as described in the original publication. It is noteworthy that, despite the initial ensemble size being set at 1000 conformations, the ultimate ensemble size varied based on the number of rotatable bonds.. For CREST, conformer generation employs the GFN2-xTB method. CREST utilizes metadynamics 158 for conformation generation and writes input and output files in the xyz file format.