The consistency metrics in Figure -e are, however, less reliable than those obtained for sulfadiazine. Figure shows well-converged marginal free energies, but Figure shows that the number of conformers identified is less consistent than in lower-dimensional cases. The number of metastable states identified as distinct conformers hovers between 22 and 25 for datasets sized 10000 and upwards. Along with a fluctuating number of conformers, Larger deviations in free energies and positions are now observed, with ∆F between cluster sets now varying by up to 5 kJmol -1 , and ∆d drifting by as much one full radian, even at large dataset sizes. Despite this drop in the quality of the results, we believe it is still remarkable that a reasonably intuitive understanding of such a high-dimensional conformational FES can be derived from a limited amount of data in a computationally accessible way, even if its value in this instance is chiefly qualitative. To further explore the consistency of the FES in Figure , Figures S2-S10 contain the FES projection for each of the smaller datasets used in the consistency analysis, allowing the evolution of this per-point FES to be observed. Inspection of this evolution in the FES seems to reveal that the majority of the fluctuations in ∆F and ∆d observed arise in higher energy conformers, with the low energy regions converging at lower N values. While we do not rigorously prove that here, it is a reasonable expectation, as lower energy regions have a high data density, resulting in free energy estimates based on a greater amount of data.