Aspartate: An interesting model for analyzing dipole‐ion and ion pair interactions through its oppositely charged amine and acid groups

Abstract 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 ( χ 1 , χ 2 ) 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.