The cation-π interaction: From structural biology to neuroreceptor binding sites

Abstract

The cation-π interaction [1,2] is a potent, noncovalent binding force that is quite prominent in structural biology and in ligand receptor interactions. Here we summarize three recent observations concerning cation-π interactions. First, we show that cation-π interactions are quite common in protein structures, with one energetically significant cation-π interaction occurring for every 77 amino acids in a protein. Second, we present computational evidence that a prototype interaction is not strongly attenuated by aqueous solvation, making it quite different than a typical salt bridge. Finally, we show how unnatural amino acid technology can be used to identify a interaction, establishing that αTrp194 is the cation-π binding site in the nicotinic acetylcholine receptor.

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