To benchmark the optimization performance of the search algorithms, we used the dataset assembled by Ebejer et al. , which consists of 708 distinct small molecules and includes ligands from the Astex Diverse Set . We filtered this set for molecules with six or fewer rotatable bonds, giving a subset of 576 molecules, including four with no rotatable bonds. For each molecule, we generated conformers using Confab as implemented in Open Babel. The conformer with the lowest MMFF94 energy across all search methods was used as the reference conformation for that molecule. This criterion differs from that usually used to assess conformer generation algorithms, namely the X-ray crystallographic structure(s) of the small molecule. This is because the conformations observed in crystal structures are not necessarily the lowest energy conformation in the force field used for the search. Our task when evaluating search methods is to find the geometry that gives the lowest energy in the function we are exploring.