Additionally, the canonical SMILES representation can generate substantially different strings for molecules that are very similar, thus making some of them more difficult to sample. To prove this, these models were sampled with replacement 2 billion times and at most only 68 % of GDB-13 could be obtained from a theoretical maximum of 87%. This maximum would be from sampling with replacement the same number of times from a theoretical ideal model that has a uniform probability of obtaining each molecule from GDB-13, thus obtaining the least possible biased output domain.