Evaluating the distribution of tyrosine and phenylalanine CH-p stacking interactions, we note that, although distinct from tryptophan interactions, these do follow the same energetic tradeoff with multiple optimal orientations (Figure ). Two representative proteins, Lactococcus lactis galactose mutarotase (PDB ID 1NSM ) and Vatairea macrocarpa seed lectin (PDB ID 4WV8 ), form CH-p stacking interactions with similar energetic favorability. The CHp interaction formed by a phenylalanine in galactose mutarotase has an interaction energy of -6.6 kcal/mol, while the one formed by a non-native tyrosine in the seed lectin is -7.0 kcal/mol (Figure ). The galactose mutarotase forms component interactions with carbon atoms C1, C3, C4, and C5, while the seed lectin forms component interactions with carbon atoms C3, C4, C5, and C6 (Figures and). Examining the structures of these protein binding pockets reinforces that carbohydrate binding is stabilized by hydrogen bonds to nearby amino acids that further influence the galactose orientation. Thus, the orientational flexibility of the CH-p stacking interactions enables the optimization of all involved interactions (Figure and Supporting Information Figures and). This analysis provides insight into the role of carbohydrate-aromatic interactions in enzyme processivity , demonstrating their ability to stabilize a bound substrate through the range of orientations that must occur during processive catalysis.