two arbitrary octapeptides and one molecule resembling a large, acidic, archipelago-type asphaltene model compound with excessively long, branched tethers. These three molecules should serve as a test of how well CREST and LEDE-CREST can explore extremely flexible single molecules with complex intramolecular non-covalent interactions, where dissociation is not a concern, as it is with clusters. For each cluster or monomer, the settings used in LEDE-CREST were the same as those developed in the methods section above. The only parameters which were varied were solvents and time limits. The monomers used in these clusters, as well as the three single molecules, are shown in Figures , 7, and 8. For comparison, ensembles were also generated from the same starting structures for each system using CREST and NCI-CREST, and various options within each which, in principle, should improve CREST's performance for difficult systems. The variations on CREST which we tested included: