A Computational Study of Cation−π Interactions vs Salt Bridges in Aqueous Media:  Implications for Protein Engineering

A direct comparison of the energetic significance of a representative salt bridge vs a representative cation−π interaction in aqueous media and in a range of organic solvents is presented using ab initio electronic structures and the SM5.42R/HF solvation model of Cramer and Truhlar. The cation−π int...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2000-02, Vol.122 (5), p.870-874
Main Authors: Gallivan, Justin P, Dougherty, Dennis A
Format: Article
Language:English
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Summary:A direct comparison of the energetic significance of a representative salt bridge vs a representative cation−π interaction in aqueous media and in a range of organic solvents is presented using ab initio electronic structures and the SM5.42R/HF solvation model of Cramer and Truhlar. The cation−π interaction shows a well depth of 5.5 kcal/mol in water, significantly larger than the 2.2 kcal/mol seen for the salt bridge. Consistent with this idea, a survey of the Protein Data Bank reveals that energetically significant cation−π interactions are rarely completely buried within proteins, but prefer to be exposed to solvent. These results suggest that engineering surface-exposed cation−π interactions could be a novel way to enhance protein stability.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja991755c