B3LYP/6-311++G** study of α- and β-d-glucopyranose and 1,5-anhydro-d-glucitol: 4C1 and 1C4 chairs, 3,OB and B3,O boats, and skew-boat conformations

Appell, Michael; Strati, Gina; Willett, J. L.; Momany, Frank A.

doi:10.1016/j.carres.2003.10.014

Cited by 121 publications

(127 citation statements)

References 41 publications

(38 reference statements)

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“…The structure of the neutral sugar molecule agrees well with the experimentally determined structure in the crystal [33] and previous density functional and MP2 calculations of the isolated molecule. [19,41,42] As seen in Table 2, the O 1 site is the most energetically favorable site for protonation in the gas phase. For comparison, the proton affinity of water obtained with the very same approach was determined to be 169 kcal mol À1 ; a recent G2 calculation [43] yielded 163 kcal mol À1 whereas the experimental value [44] is 165 kcal mol…”

Section: Resultsmentioning

confidence: 95%

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Aspects of Glycosidic Bond Formation in Aqueous Solution: Chemical Bonding and the Role of Water

Stubbs

Marx

2005

Chemistry A European J

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A model of the specific acid-catalyzed glycosidic bond formation in liquid water at ambient conditions is studied based on constrained Car-Parrinello ab initio molecular dynamics. Specifically the reaction of alpha-D-glucopyranose and methanol is found to proceed by a D(N)A(N) mechanism. The D(N) step consists of a concerted protonation of the O(1) hydroxyl leaving group; this process results in the breaking of the C(1)-O(1) bond, and oxocarbenium ion formation involving C(1)=O(5). The second step, A(N), is the formation of the C(1)-O(m) glycosidic bond, deprotonation of the methanol hydroxyl group O(m)H(m), and re-formation of the C(1)-O(5) single bond. A focus of this study is the analysis of the electronic structure during this condensed phase reaction relying on both Boys/Wannier localized orbitals and the electron localization function ELF. This analysis allows the clear elucidation of the chemical bonding features of the intermediate bracketed by the D(N) and A(N) steps, which is a non-solvent equilibrated oxocarbenium cation. Most interestingly, it is found that the oxygen in the pyranose ring becomes "desolvated" upon double bond/oxocarbenium formation, whereas it is engaged in the hydrogen-bonded water network before and after this period. This demonstrates that hydrogen bonding and thus the aqueous solvent play an active role in this reaction implying that microsolvation studies in the gas phase, both theoretical and experimental, might lead to qualitatively different reaction mechanisms compared to solution.

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Section: Resultsmentioning

confidence: 95%

“…Atoms Experimental [33] This work BLYP [41] MP2 [19] B3LYP [42] exocyclic angles Table 2. Gas phase a-d-glucopyranose proton affinities in kcal mol À1 ; see text for a discussion of the comparison with the Hartree-Fock data.…”

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confidence: 99%

Aspects of Glycosidic Bond Formation in Aqueous Solution: Chemical Bonding and the Role of Water

Stubbs

Marx

2005

Chemistry A European J

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“…The energy difference between the 4 C 1 and 1 C 4 chair conformations (about 35 kJ ⅐ mol Ϫ1 ) is also in good agreement with the corresponding range of 20 -40 kJ ⅐ mol Ϫ1 obtained from quantum-mechanical calculations. [61][62][63] Note, however, that the second most stable conformation in the present force field appears to be the B 3O boat conformation rather than the 4 C 1 chair conformation. Interactions with the solvent are likely to largely reduce the energy differences between the different conformers in aqueous solution (and might alter their relative stabilities).…”

Section: Ring Conformationmentioning

confidence: 99%

A new GROMOS force field for hexopyranose‐based carbohydrates

2005

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A new parameter set (referred to as 45A4) is developed for the explicit-solvent simulation of hexopyranose-based carbohydrates. This set is compatible with the most recent version of the GROMOS force field for proteins, nucleic acids, and lipids, and the SPC water model. The parametrization procedure relies on: (1) reassigning the atomic partial charges based on a fit to the quantum-mechanical electrostatic potential around a trisaccharide; (2) refining the torsional potential parameters associated with the rotations of the hydroxymethyl, hydroxyl, and anomeric alkoxy groups by fitting to corresponding quantum-mechanical profiles for hexopyranosides; (3) adapting the torsional potential parameters determining the ring conformation so as to stabilize the (experimentally predominant) (4)C(1) chair conformation. The other (van der Waals and nontorsional covalent) parameters and the rules for third and excluded neighbors are taken directly from the most recent version of the GROMOS force field (except for one additional exclusion). The new set is general enough to define parameters for any (unbranched) hexopyranose-based mono-, di-, oligo- or polysaccharide. In the present article, this force field is validated for a limited set of monosaccharides (alpha- and beta-D-glucose, alpha- and beta-D-galactose) and disaccharides (trehalose, maltose, and cellobiose) in solution, by comparing the results of simulations to available experimental data. More extensive validation will be the scope of a forthcoming article. (c) 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1400-1412, 2005.

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“…42-48) including carbohydrate structure and dynamics (49 -52) and carbohydrate reactivity (see for instance Refs. [53][54][55][56][57][58].…”

Section: Methodsmentioning

confidence: 99%

Substrate Distortion in the Michaelis Complex of Bacillus 1,3–1,4-β-Glucanase

Biarnés

Nieto

Planas

et al. 2006

Journal of Biological Chemistry

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The structure and dynamics of the enzyme-substrate complex of Bacillus 1,3-1,4-␤-glucanase, one of the most active glycoside hydrolases, is investigated by means of Car-Parrinello molecular dynamics simulations (CPMD) combined with force field molecular dynamics (QM/MM CPMD). It is found that the substrate sugar ring located at the ؊1 subsite adopts a distorted 1 S 3 skew-boat conformation upon binding to the enzyme. With respect to the undistorted 4 C 1 chair conformation, the 1 S 3 skew-boat conformation is characterized by: (a) an increase of charge at the anomeric carbon (C1), (b) an increase of the distance between C1 and the leaving group, and (c) a decrease of the intraring O5-C1 distance. Therefore, our results clearly show that the distorted conformation resembles both structurally and electronically the transition state of the reaction in which the substrate acquires oxocarbenium ion character, and the glycosidic bond is partially broken. Together with analysis of the substrate conformational dynamics, it is concluded that the main determinants of substrate distortion have a structural origin. To fit into the binding pocket, it is necessary that the aglycon leaving group is oriented toward the ␤ region, and the skew-boat conformation naturally fulfills this premise. Only when the aglycon is removed from the calculation the substrate recovers the all-chair conformation, in agreement with the recent determination of the enzyme product structure. The QM/MM protocol developed here is able to predict the conformational distortion of substrate binding in glycoside hydrolases because it accounts for polarization and charge reorganization at the ؊1 sugar ring. It thus provides a powerful tool to model E⅐S complexes for which experimental information is not yet available. Glycoside hydrolases (GHs)2 are the enzymes responsible for the hydrolysis of glycosidic bonds and play important biological functions such as glycan processing in glycoproteins, remodeling the cell walls, and polysaccharide modification and degradation. The reaction mechanism, a classical textbook example of enzymatic reaction, has attracted much interest because genetically inherited disorders of glycoside hydrolysis often occur and because inhibitors of these enzymes can act as new therapeutic agents for the treatment of viral infections (1, 2). Despite the large number of GHs known, classified into more than 90 families (1), the catalytic mechanism is similar. They typically operate by means of acid/base catalysis with retention or inversion of the anomeric configuration, although a different mechanism has recently been proposed for the GH family 4 (3). The acid/base reaction is assisted by two essential residues: a proton donor and a nucleophile or general base residue (4). Inverting enzymes operate by a single nucleophilic substitution, whereas retaining glycosidases follow a double displacement mechanism via formation and hydrolysis of a covalent glycosyl-enzyme intermediate. Both steps involve oxocarbenium ion-like transition states (F...

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B3LYP/6-311++G** study of α- and β-d-glucopyranose and 1,5-anhydro-d-glucitol: 4C1 and 1C4 chairs, 3,OB and B3,O boats, and skew-boat conformations

Cited by 121 publications

References 41 publications

Aspects of Glycosidic Bond Formation in Aqueous Solution: Chemical Bonding and the Role of Water

Aspects of Glycosidic Bond Formation in Aqueous Solution: Chemical Bonding and the Role of Water

A new GROMOS force field for hexopyranose‐based carbohydrates

Substrate Distortion in the Michaelis Complex of Bacillus 1,3–1,4-β-Glucanase

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