Effect of water coordination on competition between π and non-π cation binding sites in aromatic amino acids: L-phenylalanine, L-tyrosine, and L-tryptophan Li+, Na+, and K+ complexes

Quantum chemistry methods have been applied to charged complexes of the alkali metals Li+, Na+, and K+ with the aromatic amino acids (AAAs) phenylalanine (Phe), tyrosine (Tyr), and tryptophan (Trp). The geometries of 72 different complexes (Phe center dot M, Tyr center dot M, Trp center dot M, M is Li+, Na+, or K+) were completely optimized at the B3LYP/6-311+G(d,p) level of density functional theory. The solvent effect on the geometry and stability of individual complexes was studied by making use of a microsolvation model. The interaction enthalpies, entropies, and Gibbs energies of nine different complexes of the systems Phe center dot M, Tyr center dot M, and Trp center dot M (M is Li+, Na+, or K+) were also determined at the B3LYP density functional level of theory. The calculated Gibbs binding energies of the M+-AAA complexes follow the order Phe < Tyr < Trp for all three metal cations studied. Among the three AAAs studied, the indole ring of Trp is the best pi donor for alkali metal cations. Our calculations demonstrated the existence of strong cation-pi interactions between the alkali metals and the aromatic side chains of the three AAAs. These AAAs comprise about 8% of all known protein sequences. Thus, besides the potential for hydrogen-bond interaction, aromatic residues of Phe, Tyr, and Trp show great potential for pi-donor interactions. The existence of cation-pi interaction in proteins has also been demonstrated experimentally. However, more complex experimental studies of metal cation-pi interaction in diverse biological systems will no doubt lead to more exact validation of these investigations.