Exhaustive rotamer search of the 4C1 conformation of α- and β-d-galactopyranose

Vigo, Enrique A. Del; Marino, Carla; Stortz, Carlos A.

doi:10.1016/j.carres.2017.05.003

Cited by 8 publications

(5 citation statements)

References 47 publications

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“…Molecular dynamics (MD) is increasingly used to investigate carbohydrate antigen conformations in order to compare related serotypes and rationalize cross-protection phenomena. − Previous MD simulations of 4 RU of the Shigella serotype Y polysaccharide indicate a flexible backbone with a diverse array of conformations . Short simulations (60–350 ns) of 12 S.…”

Section: Introductionmentioning

confidence: 99%

Effects of Glucosylation and O-Acetylation on the Conformation of Shigella flexneri Serogroup 2 O-Antigen Vaccine Targets

2020

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Shigellosis is an enteric disease with high morbidity and mortality, particularly in developing countries. There is currently no licensed vaccine available. Most infection is caused by Shigella flexneri, of which 30 serotypes have been recognized based on O-antigen polysaccharide structure. Almost all S. flexneri serotypes share the same repeating unit backbone (serotype Y), with varying glucosylation, O-acetylation and phosphorylation. The O-antigen is the primary vaccine target; the vaccine valency (and hence cost) can be reduced by cross-protection. Our planned systematic conformational study of S. flexneri starts here with 2a, the dominant cause of infection globally. We employ microsecond molecular dynamics simulations to compare the conformation of the unsubstituted serotype Y backbone with the serogroup 2 O-antigens, to investigate the effect of glucosylation and O-acetylation (O-factor 9) on conformation. We find that serotype Y is highly flexible, whereas glucosylation in 2a restricts flexibility and induces C-curve conformations. Further, the glucose side-chains adopt two distinct conformations, corroborated by the antibody-bound crystal structure data. Additional substitution on O-3 of rhamnose A (whether O-acetylation in 2a or glucosylation in 2b) induces helical conformations. Our results suggest that the O-3-acetylated 2a antigen will elicit cross-protection against 2b, as well as other serotypes containing O-factor 9.

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Section: Introductionmentioning

confidence: 99%

Effects of Glucosylation and O-Acetylation on the Conformation of Shigella flexneri Serogroup 2 O-Antigen Vaccine Targets

2020

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“…This was further validated with the full set of isomers of the hyacinthacine family (compounds 1 – 168 ). As a general trend, the PCM series showed larger energy windows with deeper wells on the potential surface and fewer contributing conformations than those computed with SMD, consistent with previous findings . The remarkably different landscape offered by the two solvation models (more realistic in the case of SMD) was mainly related with the tendency of PCM to overestimate the stability of IHB shapes .…”

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confidence: 99%

Redefining the Impact of Boltzmann Analysis in the Stereochemical Assignment of Polar and Flexible Molecules by NMR Calculations

2019

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The in silico assignment of polyhydroxylated compounds represents a major challenge given the thus far unsolved problem of inappropriate description of the conformational amplitudes. Herein, we report a conceptually novel stochastic approach based on the creation and evaluation of random artificial ensembles, which could provide a new paradigm for computing NMR properties of flexible molecules. The strategy was successfully tested under the DP4/DP4+ platforms using a large set of compounds belonging to the hyacinthacine family.

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“…The conformers with the lowest calculated electronic-structure energy were further refined using the CBS-QB3 composite quantum-chemistry method . In the cases of some stable species for which conformer searches exist in the literature, − CBS-QB3 optimizations of the literature structures were found to have a lower electronic energy and were used instead of the initial structure. Further description of the conformer energy minimization process can be found in the Supporting Information, including a demonstration of the role of internal-hydrogen-bond alignment.…”

Section: Methodsmentioning

confidence: 99%

Monosaccharide Isomer Interconversions Become Significant at High Temperatures

McGill

Westmoreland

2018

J. Phys. Chem. A

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Quantum-chemical calculations show how low barriers to anomerization and shifting equilibria cause a significant presence of different monosaccharide isomers in high-temperature processes such as pyrolysis. The transition between isomeric forms of monosaccharides is long-studied, but examination has typically been limited to the solution phase and to pyranose isomers. Processes and rates of anomerization by reversible, gas-phase ring-opening and -closing reactions were predicted for the monosaccharides Dglucose, D-mannose, D-galactose, D-xylose, L-arabinose, and Dglucuronic acid. Structures and thermochemistry were computed for stable species and pericyclic transition states using CBS-QB3, and high-pressure-limit Arrhenius reaction parameters were predicted and fitted from 300 to 1000 K. Activation energies for the ring-opening reactions were 162−217 kJ/ mol for four-center pericyclic separation of the lactol group but were reduced by catalytic participation of a hydroxyl group within the monosaccharide or an external R−OH group represented by an explicit water molecule, reaching activation energies as low as 97 and 67 kJ/mol, respectively. Equilibrium constants implied increasing fractions of furanose and linear aldehyde anomers with increasing temperature.

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Exhaustive rotamer search of the 4C1 conformation of α- and β-d-galactopyranose

Cited by 8 publications

References 47 publications

Effects of Glucosylation and O-Acetylation on the Conformation of Shigella flexneri Serogroup 2 O-Antigen Vaccine Targets

Effects of Glucosylation and O-Acetylation on the Conformation of Shigella flexneri Serogroup 2 O-Antigen Vaccine Targets

Redefining the Impact of Boltzmann Analysis in the Stereochemical Assignment of Polar and Flexible Molecules by NMR Calculations

Monosaccharide Isomer Interconversions Become Significant at High Temperatures

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