Second, we wish to develop a simple, unambiguous protocol for identifying cation-π interactions that can be easily applied by other workers. First, we wish to develop meaningful statistics for cation-π interactions for structures within the PDB ( 21). To circumvent this problem, and to put the diverse array of potential cation-π interactions on a more nearly equal footing, we have chosen to use energy-based, rather than geometry-based, criteria in this study. The electrostatic potential surfaces of the aromatics, which control such distinctions ( 1), can be complex, and it is difficult to clearly distinguish attractive from repulsive cation-aromatic contacts using geometric criteria alone. Unlike ion pairs, for which any close contact will be energetically favorable, a cation interaction with an aromatic can be attractive or repulsive. In addition, not all cation-aromatic contacts represent energetically favorable cation-π interactions. Phe/Tyr can make such comparisons problematical. Previous protein database searches relied on geometric definitions of sidechain interactions, focusing on when a cationic sidechain displayed a certain distance/angle relationship to an aromatic sidechain. We also have documented some significant preferences for certain amino acid pairs as partners in a cation-π interaction. We find that energetically significant cation-π interactions are common in proteins-a “typical” protein will contain several.

Here we present a detailed analysis of the extent and nature of cation-π interactions that are intrinsic to a protein’s structure and likely contribute to protein stability. A number of studies have established a role for cation-π interactions in biological recognition, especially in the binding of acetylcholine ( 4, 5). Theoretical and experimental studies have shown that cation-π interactions can be quite strong, both in the gas phase and in aqueous media. In addition, the cation-π interaction ( 1– 3) is increasingly recognized as an important noncovalent binding interaction relevant to structural biology. Hydrogen bonds, salt bridges, and the hydrophobic effect all play roles in folding a protein and establishing its final structure. The three-dimensional structure of a protein is determined by a delicate balance of weak interactions.

Calculate pi of lysine