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Conformational Properties of alpha- or beta-(1 -> 6)-Linked Oligosaccharides: Hamiltonian Replica Exchange MD Simulations and NMR Experiments
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Stockholm University, Faculty of Science, Department of Organic Chemistry.
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2014 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 118, no 11, 2851-2871 p.Article in journal (Refereed) Published
Abstract [en]

Conformational sampling for a set of 10 alpha- or beta-(1 -> 6)-linked oligosaccharides has been studied using explicit solvent Hamiltonian replica exchange (HREX) simulations and NMR spectroscopy techniques. Validation of the force field and simulation methodology is done by comparing calculated transglycosidic J coupling constants and proton-proton distances with the corresponding NMR data. Initial calculations showed poor agreement, for example, with >3 Hz deviation of the calculated (3)J(H5,H6R) values from the experimental data, prompting optimization of the omega torsion angle parameters associated with (1 -> 6)-linkages. The resulting force field is in overall good agreement (i.e., within similar to 0.5 Hz deviation) from experimental (3)J(H5,H6R) values, although some small limitations are evident. Detailed hydrogen bonding analysis indicates that most of the compounds lack direct intramolecular H-bonds between the two monosaccharides; however, minor sampling of the O6 center dot center dot center dot HO2' hydrogen bond is present in three compounds. The results verify the role of the gauche effect between O5 and O6 atoms in gluco- and manno-configured pyranosides causing the omega torsion angle to sample an equilibrium between the gt and gg rotamers. Conversely, galacto-configured pyranosides sample a population distribution in equilibrium between gt and tg rotamers, while the gg rotamer populations are minor. Water radial distribution functions suggest decreased accessibility to the O6 atom in the (1 -> 6)-linkage as compared to the O6' atom in the nonreducing sugar. The role of bridging water molecules between two sugar moieties on the distributions of omega torsion angles in oligosaccharides is also explored.

Place, publisher, year, edition, pages
2014. Vol. 118, no 11, 2851-2871 p.
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
URN: urn:nbn:se:su:diva-102956DOI: 10.1021/jp412051vISI: 000333381800008OAI: oai:DiVA.org:su-102956DiVA: diva2:714865
Funder
NIH (National Institute of Health)Knut and Alice Wallenberg FoundationSwedish Research Council
Note

AuthorCount:5;

Available from: 2014-04-29 Created: 2014-04-25 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Conformations of Flexible Oligosaccharides: Molecular Simulations and NMR spectroscopy
Open this publication in new window or tab >>Conformations of Flexible Oligosaccharides: Molecular Simulations and NMR spectroscopy
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The conformational preferences of several oligosaccharides are investigated herein using a combination of NMR spectroscopy and molecular dynamics (MD) simulations, focusing on the torsion angles associated with the glycosidic linkages.

Strategies for obtaining usable J-HMBC spectra for carbons with an adjacent 13C label are described. By employing a selective pulse or a constant time modification, spectra free from interferences are obtained for site-specifically 13C labeled oligosaccharides.

Intermolecular hydrogen bonding in sucrose is investigated using MD simulations performed at different concentrations. One of the most frequent intermolecular hydrogen bonds in the simulations, O3f∙∙∙HO3g, was detected using the HSQC-TOCSY NMR experiment.

Based on MD simulations and NMR spectroscopy, the conformational ensemble for a trisaccharide segment of the LeaLex hexasaccharide is proposed to feature conformational exchange between conformations with positive and negative values for the ψ3 torsion angle in the β-D-GlcpNAc-(1→3)-β-D-Galp linkage.

Using MD simulations, the conformation of the N-acetyl group is shown to influence the glycosidic conformation at a nearby linkage in two oligosaccharides.

Short (1→6)-linked oligosaccharides are shown to exhibit conformational exchange at the ω and ψ torsion angles. Notably, the former torsion angle populates states with ψ ≈ ±90°. Conformationally sensitive homo- and heteronuclear coupling constants are determined using various NMR experiments. The experimental data, including effective distances from NOESY obtained for two of the compounds, is used to improve the representation of the ω torsion angle in the CHARMM36 force field.

Place, publisher, year, edition, pages
Stockholm: Department of Organic Chemistry, Stockholm University, 2013. 78 p.
Keyword
Carbohydrates, Oligosaccharide, Conformation, NMR spectroscopy, MD simulations
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-95480 (URN)978-91-7447-808-2 (ISBN)
Public defence
2013-12-13, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
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Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 1: Manuscript. Paper 5: Accepted. Paper 6: Manuscript.

Available from: 2013-11-21 Created: 2013-10-29 Last updated: 2015-10-06Bibliographically approved

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