It is hypothesized that quadrant bulk plays an important role in substrate orientation. To remove bias in cavity volume arising from the backbone scaffolds, octant analysis was performed for each catalyst, where only the positive-Z octants were considered for analysis (Figure ). The two backbone aryl C atoms were assigned as the XZ plane, and the probe tether atom defined the Z-axis (Figure SXb). The minimum VOCTANT was found to vary in magnitude depending on both the substituent and the backbone. The minimum VOCTANT for the BINOL backbone is larger than the SPINOL for substituents with a strict 3,5substitution pattern (Figure , red). Substituents with a 1,6-pattern generate a larger minimum octant for SPINOL backbones than BINOL (Figure , blue). Protein Binding Pockets. The binding of small molecules to protein receptors is fundamental to many biological processes. Assessment of the binding environment in protein active sites is crucial to the design of small molecule ligands and pharmaceuticals. Important features to assess in docking studies include the size and shape of the active cavity as shape matching influences binding. To illustrate the utility of SMART for quantifying protein binding pockets, the structure of the G-coupled protein receptor (GPR) was selected for analysis.