A molecular dynamics study of the complexation of tryptophan, phenylalanine and tyrosine amino acids with cucurbit[7]uril

Molecular dynamics simulations were performed in aqueous solution to elucidate an atomistic level picture of complex formation between cucurbit[7]uril (CB7) and three standard aromatic amino acids: tyrosine, tryptophan, and phenylalanine. It was found that all three amino acids formed stable host–guest complexes with CB7, in which the side chain was included inside the hydrophobic cavity and the ammonium and carboxylate groups were excluded. The major forces driving complexation, as calculated from the MM-PBSA method, were the electrostatic and van der Waal interactions. To better understand the effect of pH and the roles of the ammonium and carboxylate groups in the complexation process, simulations were performed for phenylalanine considering different protonation state (at low and high pH) as well as for the deaminated and decarboxylated forms of phenylalanine. The results showed that, compared to phenylalanine at neutral pH (exists as zwitterion), low pH resulted in an increased complex stability for the cationic form, deamination and high pH reduced the stability, while decarboxylation did not result in a significant change. Results from quantum-chemical calculations correlated well with the simulation data.