VAREA and ESA are also shown to correlate well to UCSF Chimera descriptors (Figure ). This correlation does not hold for smaller areas (Figure , gray region), attributed again to the high variability of SMART descriptors for sparse probe ensembles. We again attribute this to the area of the conformer ensemble being highly variable for sparse ensembles. VAREA is thus found to be less stable than VCAVITY, suggesting that area descriptors should only used for dense ensembles. APPLICATIONS SMART molecular descriptors are envisioned with broad applicability to the study and design of catalysts with irregular shapes. In this section, we demonstrate the utility of SMART for describing chiral phosphoric acids, enantioselective metalloenzyme catalysis, and protein side pockets by analyzing mechanistic implications of computed descriptors.