The Hydrogen-Bonding Ability of the Amino Acid Glutamine Revealed by Neutron Diffraction Experiments

Abstract

Hydrogen bonding between glutamine residues has been identified as playing an important role in the intermolecular association and aggregation of proteins. To establish the molecular mechanisms of glutamine interactions, neutron diffraction coupled with hydrogen/deuterium isotopic substitution in combination with computational modeling has been used to investigate the structure and hydration of glutamine in aqueous solution. The final structures obtained are consistent with the experimental data and provide insight into the hydrogen-bonding ability of glutamine. We find that the backbone of glutamine is able to coordinate more water molecules than the side chain, suggesting that charged groups on the glutamine molecule are more successful in attracting water than the dipole in the side chain. In both the backbone and the side chain, we find that the carbonyl groups interact more readily with water molecules than the amine groups. We find that glutamine-glutamine interactions are present, despite their low concentration in this dilute solution. This is evidenced through the occurrence of dimers of glutamine molecules in the solution, demonstrating the effective propensity of this molecule to associate through backbone-backbone, backbone-side chain, and side chain-side chain hydrogen bond interactions. The formation of dimers of glutamine molecules in such a dilute solution (30 mg/mL glutamine) may have implications in the aggregation of glutamine-rich proteins in neurological diseases where aggregation is prevalent.

Glutamine and Asparagine Side Chain Hyperconjugation-Induced Structurally Sensitive Vibrations

“…For Gln, we assume that the Gaussian centered at χ 3 ∼ −13° is the physically relevant solution based on the neutron diffraction study of Rhys et al 58 For Gln 3 and Asp 2 -Gln 10 -Lys 2 , we conclude that the Gaussians centered at negative χ 3 angles correspond to the physically relevant solutions to eq 3 because they fall within the range of χ 3 dihedral angles most commonly adopted by Gln residues that populate PPII (Φ, Ψ) angles (Figure 7c). …”

On the atomic structure of cocaine in solution

“…NDIS is a well-established technique which has been used successfully to determine the atomistic interactions between a range of molecules and water in solution. [18][19][20][23][24][25][26][27][28][29] Neutron diffraction measurements provide a direct measure of the structure in reciprocal space -the static structure factor, F(Q). F(Q) can be written as:…”

“…However, recently it has been shown that investigations into the structure and hydration of small biological molecules in solution can yield valuable insights into how these molecules may function in nature. [18][19][20] In the current work, the structure and conformation of cocaine hydrochloride has been investigated in aqueous solution on the atomic scale using a combination of neutron diffraction enhanced by isotopic substitution and computation. Understanding the details of drug interactions with aqueous environments will increase the comprehension of the mechanisms responsible for how small molecules permeate into the BBB.…”

Combining wide-angle and small-angle scattering to study colloids and self-assembly

“…Both SANS and wideangle scattering studies were carried out on the same solutions and although the formation of larger transient clusters of proline [38,39] and glutamine [40] were observed during modelling of the wide angle scattering data and in MD simulations, no larger scale structures were found in the SANS data.…”