Experimental Evaluation of CH–π Interactions in a Protein Core

CH-π stacks up! Using the protein α(2) D as a model system, we estimate that a CH-π contact between cyclohexylalanine (Cha) and phenylalanine (F) contributes approximately -0.7 kcal mol(-1) to the protein stability. The stacking F-Cha pairs are sequestered in the core of the protein, where water interference does not exist (see figure). Therefore, the observed energetic gain should represent the inherent magnitude and upper limit of the CH-π interactions.