Molecular Dynamics and Conformational Kinetics of Mono‐ and Disaccharides in Aqueous Solution

Abstract

Acoustical attenuation spectra between 10 kHz and 2 GHz, complex dielectric spectra between 300 kHz and 40 GHz, and time-resolved non-equilibrium measurements are reported for aqueous solutions of various mono- and disaccharides with and without 2:1 valent salts. The spectra reveal a variety of relaxation regimes with relaxation times between 1 micros and 10 ps. In addition, the time-resolved observations enable the study of the mutarotation with relaxation times on the order of 10(3) s. Variation of the concentration and temperature as well as a careful choice of the saccharides allow a discussion of the relaxation processes in terms of a chair-chair ring inversion, two modes of pseudorotation, an exocyclic hydroxymethyl group rotation, a carbohydrate-carbohydrate association, and, in the disaccharide solutions, a rotation of the rings relative to another. Salt-containing solutions show also relaxation phenomena reflecting different steps cation-carbohydrate association and variations in the carbohydrate conformational isomerizations and associations due to interactions with cations.

Conformational properties of glucose-based disaccharides investigated using molecular dynamics simulations with local elevation umbrella sampling

“…For completeness, mutarotation (ring opening and randomization of the anomeric configuration for reducing residues) is associated with timescales 79,[284][285][286][287][288][289][290] in the order of 10 3 s.…”

“…This choice of subspace for the LEUS enhancement is justified by the previous observation 58, 59 that torsional transitions around all other exocyclic dihedral angles occur in the $30 ps to ns range, that is, these degrees of freedom are appropriately sampled on the 50 ns timescale, even in the absence of sampling enhancement. In contrast, conformational transitions of the glucopyranose rings (from the most stable 4 C 1 chair to the inverted 1 C 4 chair, or to boat or skew-boat conformations) are much slower, with timescales in the order of 15-1000 ns (estimated 71 based on the present force field) or 50-1000 ns (ultrasonic-relaxation spectroscopy [76][77][78][79] and NMR 80 measurements on glucopyranose, estimate for penta-acetylated idopyranose 81 ). However, the corresponding reverse transitions are fast, with timescales in the ps to ns range (estimated 71 based on the present force field).…”

“…For these disaccharides, the comparison of the free-energy differences and barriers associated with transitions involving the / and w dihedral angles does not reveal any clear systematic trend. In particular, for the disaccharides involving an equatorial-equatorial linkage, the metastable state involving a transition around / may be lower (S, L), equally high (T b,b ), or higher (C) in free energy compared to the one involving a transition around w. Experimentally, ultrasonic relaxation experiments suggest a timescale of about 10 ns for the relative rotation of the two pyranose rings in disaccharides, 78,79,[217][218][219] which is about one order of magnitude faster than the timescales indicated above. The cause of this discrepancy probably resides in the force-field employed in the present simulations.…”

Amylose folding under the influence of lipids

“…8,9 Molecular dynamics (MD) simulations have proven to be a useful tool for providing a link between dynamics and structure. Many force fields have been extensively parameterized for carbohydrates, [10][11][12][13][14][15][16][17] and have been used to provide details of the structure and dynamics at an all atom (AA) level; for example to explore the ring puckering of glucose, 18,19 conformational changes in disaccharides and trisaccharides. 11,[20][21][22] However, previous MD studies of amylose have mainly dealt with small amylose fragments in water or studies of V-amylose in low polarity solvents.…”

“…Many force fields have been extensively parameterized for carbohydrates, [10][11][12][13][14][15][16][17] and have been used to provide details of the structure and dynamics at an all atom (AA) level; for example to explore the ring puckering of glucose, 18,19 conformational changes in disaccharides and trisaccharides. 11,[20][21][22] However, previous MD studies of amylose have mainly dealt with small amylose fragments in water or studies of V-amylose in low polarity solvents. [23][24][25] The object of the present study was to deepen the understanding of the structure and formation of V-amylose inclusion complexes in view of its anticipated use as a delivery system of long chain fatty acids and other nutraceuticals.…”