We first analyzed the number of conformers sampled by systematic search (Confab). Fig. shows that up to 10 6 of conformers were explored for molecules with six rotatable bonds. For molecules with four or more rotatable bonds, the median number of conformers generated was approximately 10 3 to 10 4 . Cochliodinol has six rotatable bonds and had generated over one million of conformers, with 750, 402 conformers retained, and the lowest energy of 146.04 kcal/mol. Bayesian optimization algorithm, on the other hand, required only 10 2 evaluations to obtain low energy conformations, and the best conformation out of five trials had an almost identical energy of 146.13 kcal/mol. This highlights the power of BOA, and we will show that BOA gives good performance in general despite using orders of magnitude fewer energy evaluations.