SMART descriptors were found to capture salient trends across BINOL and SPINOL CPAs. Lower VCAVITY in SPINOL catalysts supports the prevalence of higher selectivity compared to BINOL catalysts. SMARTpy was also demonstrated with a GPR101-Gs side binding pocket. The hindrance of the N-terminus and transmembrane domain are emphasized, suggesting that favorable non-covalent interactions are likely responsible for the initial procedure of small molecule binding. Finally, two enzymes used for different selective transformations are shown to differ in the distal region of the porphyrin cavity. The more hindered distal cavity observed in P411-PFA is hypothesized to constrain the approach of substrates to the Fe-carbene, directing selectivity for C-H functionalization.