Interaction between the guanidinium cation and aromatic amino acids

Area of Science:

• Computational Chemistry
• Biomolecular Interactions
• Quantum Chemistry

Background:

• The guanidinium cation is a key functional group in biological systems, particularly in amino acids like arginine.
• Understanding its interactions with aromatic amino acids (phenylalanine, tyrosine, tryptophan) is crucial for molecular recognition and drug design.

Purpose of the Study:

• To computationally investigate the interaction energies and structural preferences between the guanidinium cation and phenylalanine, tyrosine, and tryptophan.
• To elucidate the energetic contributions governing the stability of different complexation structures.

Main Methods:

• Utilized a variety of computational chemistry methods for interaction studies.
• Employed the coupled cluster singles, doubles, and triples (CCSD(T)) method extrapolated to the complete basis set limit for benchmark calculations.
• Analyzed electrostatic, induction, dispersion, repulsion, and deformation energy contributions.

Main Results:

• Benchmark complexation energies were determined: -123.0 kJ/mol (Phe), -124.4 kJ/mol (Tyr), and -134.2 kJ/mol (Trp).
• Most stable structures involve neutral, folded amino acids interacting with the cation via carboxyl, amino, and aromatic ring contacts.
• Complexes with zwitterionic amino acids exhibit comparable stability to neutral forms, arising from a balance of large electrostatic/induction effects and significant deformation costs.

Conclusions:

• The relative stability of guanidinium-amino acid complexes is governed by a delicate interplay of energetic contributions.
• Cation-π interactions in folded structures, along with induction and dispersion forces, contribute to the stability of the most favored complexes.
• Both neutral folded and zwitterionic forms of phenylalanine, tyrosine, and tryptophan can form highly stable complexes with the guanidinium cation.