The potential energy surface of methyl 3‐<i>O</i>‐(α‐<scp>D</scp>‐mannopyranosyl)‐α‐<scp>D</scp>‐mannopyranoside in aqueous solution: Conclusions derived from optical rotation

Stevens, Eugene S.

doi:10.1002/bip.360341010

Cited by 12 publications

(6 citation statements)

References 36 publications

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“…Beginning with the III-OCH 3 linkage, these authors noted a discrepancy in measured correlation times for the methyl group and postulated that this could arise from additional motions of this group that were not included in their treatment of the data. More recently, results of optical rotation studies on methyl ␣-D-mannopyranoside found that including a population of a ϭ 180°state of 10 -20% (in addition to the ϭ 60°s tate) for the methoxy linkage was able to bring the calculated values of the molar rotation into agreement with those experimentally observed (Stevens et al, 1989;Stevens, 1994). These results agree well with our model, which supports a minor population of a ϭ 150°state of less than 35%.…”

Section: Comparison To Similar Structuressupporting

confidence: 90%

“…Later studies using MD simulations, both in vacuo (Balaji et al, 1994) and including explicit solvent (Homans, 1990), along with other studies using proton relaxation measurements in partially deuterated samples (Hricovíni et al, 1992) all found evidence of internal motion at this linkage, suggesting that both of the previously identified states may be sampled in solution. More recent studies using optical rotation techniques (Stevens, 1994), molecular mechanics modeling (Dowd et al, 1995), and circular dichroism (Arndt and Stevens, 1996) have indeed concluded that states near (80°, Ϫ160°) and (80°, Ϫ80°) are likely to be equally populated in solution. These studies also predicted a small population (ϳ10%) of a state near (160°, Ϫ80°).…”

Section: Comparison To Similar Structuresmentioning

confidence: 99%

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Solution Conformations of a Trimannoside from Nuclear Magnetic Resonance and Molecular Dynamics Simulations

Sayers

Prestegard

2000

Biophysical Journal

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N-linked oligosaccharides often act as ligands for receptor proteins in a variety of cell recognition processes. Knowledge of the solution conformations, as well as protein-bound conformations, of these oligosaccharides is required to understand these important interactions. In this paper we present a model for the solution conformations sampled by a simple trimannoside, methyl 3, 6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside, which contains two of the most commonly found glycosidic linkages in N-linked oligosaccharides. This model was derived from simulated annealing protocols incorporating distance restraints extracted from NOESY spectra along with torsional restraints computed from three-bond (1)H-(13)C coupling constants measured across the glycosidic bonds. The model was refined in light of unrestrained molecular dynamics simulations conducted in the presence of solvent water. The resulting model depicts a molecule undergoing conformational averaging in solution, adopting four major and two minor conformations. The four major conformations arise from a pair of two-state transitions, one each at the alpha(1-->3) and alpha(1-->6) linkages, whereas the minor conformations result from an additional transition of the alpha(1-->6) linkage. Our data also suggest that the alpha(1-->3) transition is fast and changes the molecular shape slightly, whereas the alpha(1-->6) is much slower and alters the molecular shape dramatically.

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Section: Comparison To Similar Structuressupporting

confidence: 90%

Section: Comparison To Similar Structuresmentioning

confidence: 99%

Solution Conformations of a Trimannoside from Nuclear Magnetic Resonance and Molecular Dynamics Simulations

Sayers

Prestegard

2000

Biophysical Journal

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“…The current solvated MD data indicate that the A-(1→3) linkage between A-4′ is more flexible than the 4-3 linkage, as we would expect that the more internal location of the 4-3 linkage within Man 9 GlcNAc 2 would make it more inflexible. Flexibility of the A-(1→3) linkage in the related mannose disaccharide is consistent with experimental optical rotation measurements [36]. A crude estimate of the increased flexibility of the A-4′ linkage is provided by the relatively high values for the standard deviations in the values of the glycosidic angles (Ϫ22Ϯ 22°, Ϫ30Ϯ 16°) for this linkage.…”

Section: Conformational Analysis By Molecular Dynamics Simulationsupporting

confidence: 83%

The high degree of internal flexibility observed for an oligomannose oligosaccharide does not alter the overall topology of the molecule

Woods¹,

Pathiaseril²,

Wormald³

et al. 1998

European Journal of Biochemistry

138

141

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The conformational properties of oligosaccharides are important in determining their biological properties, such as recognition by proteins. The structural and dynamic properties of many oligosaccharides are poorly understood both because of a lack of experimental data (usually obtained from solution NMR parameters) and because of gross approximations frequently invoked in theoretical models. To characterise the oligomannose oligosaccharide Man,GlcNAc2 we have acquired a more extensive NMR data set and performed the first unrestrained molecular dynamics (MD) simulation in water of this large oligosaccharide (employing the GLYCAM_93 parameter set with the AMBER force field). Good agreement is seen between the computed dynamics data and the results of both an isolated spin pair (ISPA) analysis of short mixing time NOE data and NOE build-up curves for mixing times from 100 to 2000 ms. The number of experimental conformational constraints obtained in this study are in principle sufficient to fully define a rigid structure. The fact that this could not be done indicates a high degree of internal flexibility and/or the presence of multiple conformations about the glycosidic linkages. Independently, the same conclusions are reached from an analysis of the MD results. In addition, the theoretical results allow the overall topology of the molecule and its intra-molecular and solvent-mediated hydrogen bonding pattern to be defined. Extensive re-organisation of solvent and inter-residue hydrogen bonds is shown to be required for significant conformational changes to occur, resulting in relatively long life-times for distinct glycosidic linkage conformations, despite the high local flexibility of the glycosidic linkages. This factor is also seen in the overall topology of the molecule, where the considerable internal flexibility is not translated into gross changes in structure. The control exerted by the solvent over both the flexibility and overall topology of an oligosaccharide has important implications for recognition processes and for the conformational properties of glycans attached to glycoproteins.

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“…Oligosaccharides containing α-linked mannose residues have previously been studied by molecular modeling in both vacuum and water . Modeling studies have also been combined with NMR relaxation, , optical rotation, and X-ray crystallography data . The results from these studies indicate that a predominant conformation exists for both the α(1→2) and the α(1→3) linkages, but minor populations of other conformers could not be ruled out on the basis of the experimental data used.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Aqueous Molecular Dynamics with NMR Relaxation and Residual Dipolar Couplings Favors Internal Motion in a Mannose Oligosaccharide

et al. 2001

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An investigation has been performed to assess how aqueous dynamical simulations of flexible molecules can be compared against NMR data. The methodology compares state-of-the-art NMR data (residual dipolar coupling, NOESY, and (13)C relaxation) to molecular dynamics simulations in water over several nanoseconds. In contrast to many previous applications of residual dipolar coupling in structure investigations of biomolecules, the approach described here uses molecular dynamics simulations to provide a dynamic representation of the molecule. A mannose pentasaccharide, alpha-D-Manp-(1-->3)-alpha-D-Manp-(1-->3)-alpha-D-Manp-(1-->3)-alpha-D-Manp-(1-->2)-D-Manp, was chosen as the model compound for this study. The presence of alpha-linked mannan is common to many glycopeptides, and therefore an understanding of the structure and the dynamics of this molecule is of both chemical and biological importance. This paper sets out to address the following questions. (1) Are the single structures which have been used to interpret residual dipolar couplings a useful representation of this molecule? (2) If dynamic flexibility is included in a representation of the molecule, can relaxation and residual dipolar coupling data then be simultaneously satisfied? (3) Do aqueous molecular dynamics simulations provide a reasonable representation of the dynamics present in the molecule and its interaction with water? In summary, two aqueous molecular dynamics simulations, each of 20 ns, were computed. They were started from two distant conformations and both converged to one flexible ensemble. The measured residual dipolar couplings were in agreement with predictions made by averaging the whole ensemble and from a specific single structure selected from the ensemble. However, the inclusion of internal motion was necessary to rationalize the relaxation data. Therefore, it is proposed that although residual dipolar couplings can be interpreted as a single-structure, this may not be a correct interpretation of molecular conformation in light of other experimental data. Second, the methodology described here shows that the ensembles from aqueous molecular dynamics can be effectively tested against experimental data sets. In the simulation, significant conformational motion was observed at each of the linkages, and no evidence for intramolecular hydrogen bonds at either alpha(1-->2) or alpha(1-->3) linkages was found. This is in contrast to simulations of other linkages, such as beta(1-->4), which are often predicted to maintain intramolecular hydrogen bonds and are coincidentally predicted to have less conformational freedom in solution.

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The potential energy surface of methyl 3‐O‐(α‐D‐mannopyranosyl)‐α‐D‐mannopyranoside in aqueous solution: Conclusions derived from optical rotation

Cited by 12 publications

References 36 publications

Solution Conformations of a Trimannoside from Nuclear Magnetic Resonance and Molecular Dynamics Simulations

Solution Conformations of a Trimannoside from Nuclear Magnetic Resonance and Molecular Dynamics Simulations

The high degree of internal flexibility observed for an oligomannose oligosaccharide does not alter the overall topology of the molecule

Comparison of Aqueous Molecular Dynamics with NMR Relaxation and Residual Dipolar Couplings Favors Internal Motion in a Mannose Oligosaccharide

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