A theoretical study of potassium cation binding to prolylglycine (PG) and glycylproline (GP) dipeptide

The interaction between potassium cation (K+) and proline-containing dipeptides, prolylglycine (PG) and glycylproline (GP), is studied using density functional theory. We found that prolylglycine and its K+ bound complexes (K+-PG) closely resemble that of the analogous glycylglycine (GG) and its K+ bound complexes (K+-GG) reported previously. For glycylproline (GP), as the nitrogen of the amide (peptide) bond is part of the proline pyrrolidine ring, the structures, relative stabilities of conformers, and the preferred mode of K+ binding are different from those of prolylglycine (PG) and glycylglycine (GG). Our study suggests that even though replacing glycine with a proline residue enhances the stability of the zwitterionic mode of binding, the most stable mode of K+ binding remains to be charge-solvated in nature in both PG (K+ binds bidentately to amide and C-terminal carbonyl oxygens) and GP (K+ binds tridentately to amide oxygen, C-terminal carbonyl oxygen and N-terminal amino nitrogen), and the K+ affinities estimated for PG and GP are 154 kJ mol−1 and 159 kJ mol−1, respectively.