Theoretical Study on Conformation-Dependent Properties of the Three Aromatic Amino Acids

Abstract

Study on conformation-dependent properties of the three aromatic amino acids (L-phenylalanine, L-tyrosine and L-tryptophan) in neutral and radical cations has been performed by using density functional theory (DFT) with a new density functional M05-2X, which is applicable to molecular systems with noncovalent long-range interactions such as intramolecular hydrogen bonding. First of all, M05-2X is applied to several simple cromophores in order to verify reliability of the method as well. The results obtained from M05-2X are compared with those estimated by using the conventional DFT (B3LYP) and can explain the correspondence between the observed and predicted chromophores without ambiguity. On the other hand, a considerable discrepancy between the predicted results from DFT (B3LYP) and experimental ones is found. This suggests that noncovalent long-range effects should be included for accuracy of calculation. Optimized geometrical structures for both the neutral and cationic conformers of the amino acids are evaluated with those DFT methods and the procedure of conformerization for L-phenylalanine conformers in neutral is indicated from the results of intrinsic reaction coordinate (IRC) profile. As described above, M05-2X method successfully produces experimental adiabatic and vertical ionization energies for all the three aromatic amino acids, whereas B3LYP functional yields significantly lower ionization energies from the observed ones by 0.2 ~ 0.3 eV. Charge distributions in the cationic conformers are estimated by using natural bond orbital (NBO) analysis. All the conformers of L-tyrosine and L-tryptophan become charge localization when they are ionized regardless of the type of intramolecular hydrogen bonding, unlike the case of L-phenylalanine that was clarified earlier by other studies. Their charge distribution analysis helps dynamics of charges in proteins to be understood because the three aromatic amino acids play a role as chromophores in biomolecules. A simple model is employed in order to figure out different degrees of charge localization among all the three aromatic amino acids. The basic concept of the model starts from postulation that the aromatic amino acid consists of two sub-moieties of distinct cationic core: the backbone and aromatic residue. The difference in adiabatic ionization energy between these two sub-moieties is found to govern the degree of charge localization. Here it is illuminated theoretically that there exists considerable correlation between conformation-dependent property and ionization energy for the three aromatic amino acids.