Molecular Dynamics and NMR Study of the α(1→4) and α(1→6) Glycosidic Linkages:  Maltose and Isomaltose

Abstract

We report the results of molecular dynamics (MD) simulations compared with NMR relaxation experiments for maltose and isomaltose. The (Φ,Ψ) adiabatic map for maltose shows a single principal energy well, while the (Φ,Ψ,Ω) map of isomaltose reveals multiple low energy minima separated by significant barriers (9 kcal/mol) in some cases. The greater accessible conformational space of the α(1→6) linkage appears to make it more flexible as compared with the α(1→4) linkage, especially in the presence of water. Correlation times for glycosidic dihedral angle fluctuations are significantly shorter in the case of isomaltose. While the generalized order parameters calculated from the simulations do not show a large difference in the spatial restriction of the motion, they are nonetheless generally lower for isomaltose. The time scales of the overall rotational motion (τM) and the local molecular motion (τe) are similar for both maltose and isomaltose. This makes reliable estimates of order parameters from experimental relaxation data (using the model-free formalism) unfeasible. We were, however, able to show that T 1 relaxation times calculated from the MD data agree well with the experimental values. As a further measure of solution flexibility, three-dimensional water distributions were calculated about each disaccharide. These demonstrate that the more rigid maltose solute causes the water to adopt a more localized structure about it. Because of its extended structure, isomaltose appears to make a greater number of hydrogen bonds to water.

Conformation and Dynamics at a Flexible Glycosidic Linkage Revealed by NMR Spectroscopy and Molecular Dynamics Simulations: Analysis of β-l-Fucp-(1→6)-α-d-Glcp-OMe in Water Solution

“…67 However, as in the present case, effects of anisotropic diffusion must be separated from contributions due to internal motion before conclusions about the latter can be drawn.…”

Effect of methylation on the stability and solvation free energy of amylose and cellulose fragments: a molecular dynamics study

“…5 (see Section 4) and compared with the values derived from experimental relaxation parameters. 13 As can be seen from Figure 3, the values for the C-H vectors in the six-membered rings are relatively large indicating that maltose and its sixmembered glycosyl unit are quite rigid. Due to greater freedom of motion, in the simulation the C-6-H-6 and C-6 0 -H-6 0 vectors have much lower order parameters than those within the ring, while in the experiment the C-6-H-6 and C-6 0 -H-6 0 vectors have order parameters comparable to those within the ring.…”

“…Molecular dynamics (MD) simulation studies of carbohydrates in the literature 10;11 deal with maltose or cellobiose composed of two glucose units [12][13][14][15][16] or with cyclic chains including a-, b, and c-cyclodextrins [17][18][19][20][21][22][23] as well as the single glucose units of a-and b-anomers. 15;24;25 However, there are only a few studies dealing with longer amylose or cellulose chains.…”

Vacuum-ultraviolet circular dichroism study of oligosaccharides using a synchrotron-radiation spectrophotometer

“…1). On the other hand, Best et al found that isomaltose exhibited multiple low-energy minima, with more flexible and more extended conformations in water compared with maltose in the MD simulations and NMR relaxation experiments [4], indicating that the torsion angle of glycosidic linkages in isomaltose is rather variable.…”