Simple Cation-π Interaction between a Phenyl Ring and a Protonated Amine Stabilizes an &alpha-Helix in Water.

Cation-π interactions have been proposed to be important contributors to protein structure and function. In particular, these interactions have been suggested to provide significant stability at the solventexposed surface of a protein. We have investigated the magnitude of cation-π interactions between phenylalanine (Phe) and lysine (Lys), ornithine (Orn), and diaminobutanoic acid (Dab) in the context of an α-helix and have found that only the Phe···Orn interaction provides significant stability to the helix, stabilizing it by -0.4 kcal/mol. This interaction energy is in the same range as a salt bridge in an α-helix, and equivalent to the recently reported Trp···Arg interaction in an α-helix, despite the fact that Trp···guanidinium interactions have been proposed to be stronger than Phe···ammonium interactions. These results indicate that even the simplest cation-π interaction can provide significant stability to protein structure and demonstrate the subtle factors that can influence the observed interaction energies in designed systems. [ABSTRACT FROM AUTHOR]