title: Simple cation-pi interaction between a phenyl ring and a protonated amine stabilizes an alpha-helix in water.
abstract: Cation-pi 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 solvent-exposed surface of a protein. We have investigated the magnitude of cation-pi interactions between phenylalanine (Phe) and lysine (Lys), ornithine (Orn), and diaminobutanoic acid (Dab) in the context of an alpha-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 alpha-helix, and equivalent to the recently reported Trp...Arg interaction in an alpha-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-pi interaction can provide significant stability to protein structure and demonstrate the subtle factors that can influence the observed interaction energies in designed systems.
authors.affiliation: Department of Chemistry, Venable and Kenan Laboratories, CB 3290, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Lun K
authors.initials: LK
authors.lastname: Tsou
authors.forename: Chad D
authors.initials: CD
authors.lastname: Tatko
authors.forename: Marcey L
authors.initials: ML
authors.lastname: Waters
mesh_terms: D000595:Amino Acid Sequence; D002412:Cations; D002942:Circular Dichroism; D008239:Lysine / Q000737:chemistry*; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D009952:Ornithine / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry*; D017433:Protein Structure, Secondary; D014867:Water / Q000737:chemistry*
chemical_list: D002412:Cations; D010455:Peptides; D014867:Water; D010649:Phenylalanine; D009952:Ornithine; D008239:Lysine