Aspartate: An interesting model for analyzing dipole-ion and ion pair interactions through its oppositely charged...

Anionic species of aspartic acid, Asp^- , having a zwitterionic backbone and a deprotonated side chain, appears to be a good example for analyzing dipole-ion and ion pair interactions. Density functional theory calculations were herein performed to investigate the low energy conformers of Asp^- embedded in a dielectric continuum modeling an aqueous environment, through a scan of the potential energy as a function of the side chain (χ₁ , χ₂ ) torsion angles. The most energetically favorable conformers having g⁺ g^- and g^- g⁺ side chain orientations are found to be stabilized by charge-enhanced intramolecular H-bonding involving the positively charged ( $$ ) and the two negatively charged (COO^- ) groups. These conformers were further used to analyze Asp^-  + nW clusters (W: water, n = 1 or 3), and Asp^- /Asp^- pair formation. COO^- groups were found to be the most attractive sites for hosting a water molecule (binding energy: -6.0 ± 1.5 kcal/mol), compared to $$ groups (binding energy: -4.7 ± 1.1 kcal/mol). Energy separation between g⁺ g^- and g^- g⁺ conformers increases upon explicit hydration. Asp^- /Asp^- ion pairs, stabilized by the interaction between the $$ group of a partner and the COO^- group of the other, shows a quite constant binding energy (-8.1 ± 0.2 kcal/mol), whatever the pair type, and the relative orientation of the two interacting partners. This study suggests a first step to achieve a more realistic image of intermolecular interactions in aqueous environment, especially upon increasing concentration. It can also be considered as a preliminary attempt to assess the interactions of the Lys⁺ …Asp^- /Glu^- ion pairs stabilizing intra- and interchain interactions in proteins.