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 (NH + 3 ) 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 NH + 3 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 NH + 3 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 intraand interchain interactions in proteins. K E Y W O R D S aspartic acid, charge-enhanced H-bonding, density functional theory calculations, dipole-ion interactions, energy landscape, hydration, ion pair interactions

Hydration effects on the vibrational properties of carboxylates: From continuum models to QM/MM simulations

“…The choice of the methods was based on recent work that has already been published in the literature: DFT using the M05-2X 58 functional and the cc-pVDZ basis set, 59 used by Sutton et al for carboxylates among which succinate; 41 DFT with the B3LYP 60 functional and the 6-311++G(d,p) basis set, 61,62 used by Hernández et al for aspartate. 45 Results obtained with these methods have been compared with PM6 46 semiempirical calculations. Two different continuum models of solvation were used, namely the solvation model density (SMD) 63 and the polarizable continuum model (PCM).…”

“…In a bottom‐up approach, first we performed electronic structure calculations using a continuum representation of the water solvent. We then included a number of water molecules corresponding to the number of polar groups (two for succinate, three for aspartate) 41,45 in a continuum and, finally, once the PM6 46 semiempirical level was validated through comparison with density functional theory (DFT) calculations, we ran hybrid quantum mechanics‐molecular mechanics (QM/MM) molecular dynamics (MD). Such an approach allowed us to investigate the local water network and the conformational space of the solute (by umbrella sampling 47 along the CCCC dihedral) in the presence of an explicit solvent.…”

Multiconformational analysis of tripeptides upon consideration of implicit and explicit hydration effects

“…The choice of an amide group instead of a routinely used acid group is basically for avoiding the formation of folded structures induced by attractive electrostatic interactions between zwitterionic (NH3 + /COO -) end groups in an aqueous media [40]. It should be noted that a number of neurohypophyseal hormones, such as vasopressin and oxytocin, have an amide group at their C ter side [41][42][43][44].…”

“…1). Taking into account the protocols described in the previous reports on the privileged hydration sites of amino acids [40,61], our aim was to find a minimal number of water molecules allowing achievement of an optimal interaction with all the aforementioned polar sites. As a consequence, two water molecules were used for hydrating the two terminal NH3 + and NH2 groups, and three others for interacting each one with the neighbouring C=O and N-H groups.…”

Guanidinium–amino acid hydrogen-bonding interactions in protein crystal structures: implications for guanidinium-induced protein denaturation

“…, Lys, Arg and protonated His side chain headgroups) and Gdm + . In contrast, like the interaction between main-chain NH 3 + and side-chain COO − groups observed in the Asp–Asp dimer, 48 Gdm + can favorably interact with the COO − groups of acidic amino acids. Similarly, DFT calculations suggested that Gdm + can form both cation–π and HB interactions with the aromatic Phe, His, Trp and Tyr, but that His forms only weak complexes due to its lower aromaticity.…”