A computational insight into the interaction of methylated lysines with aromatic amino acid cages

Posttranslational lysine methylations in histone proteins are recognized by specific reader proteins. The interaction proceeds through the binding of methylated lysine to the aromatic cages created by the combinations of tryptophan and/or tyrosine and/or phenylalanine, and it is specific to the degree of methylation of lysine residue. The chemical recognition is based on cation-π interaction between positively charged lysine and the π system of the aromatic groups. In this study, the energetics of the binding of model methylated Lys to the model aromatic amino acids as well as aromatic cages are investigated with density functional theory calculations. Molecular orbitals corresponding to the bound complexes and separate lysine and aromatic amino acid components are analyzed. Finally, using single-point energy calculations, the feasibility of comparing binding energies/affinities of methylated lysines with different methylation degrees is shown, using available crystal structures of the bound model complexes.