Sucrose in aqueous solution revisited, Part 2: Adaptively biased molecular dynamics simulations and computational analysis of NMR relaxation

Abstract

We report 100 ns molecular dynamics simulations, at various temperatures, of sucrose in water (with concentrations of sucrose ranging from 0.02 to 4 M), and in a 7:3 water-DMSO mixture. Convergence of the resulting conformational ensembles was checked using adaptive-biased simulations along the glycosidic φ and ψ torsion angles. NMR relaxation parameters, including longitudinal (R1) and transverse (R2) relaxation rates, nuclear Overhauser enhancements (NOE), and generalized order parameter (S2) were computed from the resulting time-correlation functions. The amplitude and time scales of molecular motions change with temperature and concentration in ways that track closely with experimental results, and are consistent with a model in which sucrose conformational fluctuations are limited (with 80–90% of the conformations having φ – ψ values within 20° of an average conformation), but with some important differences in conformation between pure water and DMSO-water mixtures.

Direct Evidence for Hydrogen Bonding in Glycans: A Combined NMR and Molecular Dynamics Study

“…However, high sample concentration and using mixed solvents are not desirable because these conditions may favor conformations not present in dilute water solution; therefore, the obtained data may not be relevant to glycan structure under physiological conditions. 42 Alternatively, working under super-cooled conditions (255 K 17 ) is a better approach, because it favors the observation of more stable conformations already present in solution. However, one seeks to perform structural studies at, or closer to, physiological conditions because it affords a more relevant interpretation of structure-function relationships in a biological context.…”

Sucrose in aqueous solution revisited, Part 1: Molecular dynamics simulations and direct and indirect dipolar coupling analysis

“…We mainly focused on the global conformation change from the glycosidic linkage although we also consider the analysis of local fluctuations such as intramolecular hydrogen bond and sugar puckering. In a second article41 we will report systems with varying concentrations of sucrose in water and water‐DMSO mixtures, for comparison with NMR relaxation measurements.…”

Using molecular dynamics trajectories to predict nuclear spin relaxation behaviour in large spin systems

“…We tested the proposed methods on aqueous sucrose (GLYCAM06 force field [22]) with OPC [5] and TIP5P [23] water. Conformational mobility in sucrose is well researched, particularly by 13 C spin relaxation measurements interpreted using isolated spin-pair approximations [24][25][26]. Here, we will focus on the less straightforward but more informative 1 H-1 H nuclear Overhauser effect (NOE) that probes the contacts between the H1 anomeric proton (Figure 1) of glucose and H11,12 protons of fructose positioned across the glycosidic bond connecting glucose and fructose residues.…”