The energy function explored by Bayesian optimization algorithm could be the result of a multi-step, "black box" protocol. For example, each energy value at a given point in the search space could be the result of a short MMFF94 optimization -not just a single-point energy calculation as used here (i.e. the common "fixedrotor" approximation) . In such a scenario, BOA would "learn" the torsion angles that minimize steric clashes in the molecule. This would not be comparable with the systematic Confab and uniform random search methods investigated here, because changes in bond lengths and bond angles introduced by the MMFF94 optimization would also change the energy landscape being optimized. Bond lengths and bond angles are never changed by Confab or torsion-driven uniform random search. This makes it hard to compare our current results with other stochastic search methods such as distance geometry, constrained distance geometry, and molecular mechanics energy minimization provided by tools such as RDKit. We intend to complete a comprehensive comparison with free, open-source, and commercial toolkits in the future, but note that at present among common tools, only the BOA strategy seeks to find the lowest energy conformer.