Computerized Molecular Modeling of Carbohydrates.

Computerized molecular modeling continues to increase in capability and applicability to carbohydrates. This chapter covers nomenclature and conformational aspects of carbohydrates, perhaps of greater use to computational chemists who do not have a strong background in carbohydrates, and its comments on various methods and studies might be of more use to carbohydrate chemists who are inexperienced with computation. Work on the intrinsic variability of glucose, an overall theme, is described.

Quantum mechanics models of the methanol dimer: OH⋯O hydrogen bonds of β-d-glucose moieties from crystallographic data.

The interaction of two methanol molecules, simplified models of carbohydrates and cellulose, was examined using a variety of quantum mechanics (QM) levels of theory. Energy plots for hydrogen bonding distance (H⋯O) and angle (OH⋯O) were constructed. All but two experimental structures were located in stabilized areas on the vacuum phase energy plots.

Conformational analysis of cellobiose by electronic structure theories.

Adiabatic Φ/ψ maps for cellobiose were prepared with B3LYP density functional theory. A mixed basis set was used for minimization, followed with 6-31+G(d) single-point calculations, with and without SMD continuum solvation. Different arrangements of the exocyclic groups (38 starting geometries) were considered for each Φ/ψ point.

Computerized molecular modeling of carbohydrates.

Computerized molecular modeling continues to increase in capability and applicability to carbohydrates. This chapter covers nomenclature and conformational aspects of carbohydrates, perhaps of greater use to carbohydrate-inexperienced computational chemists. Its comments on various methods and studies might be of more use to computation-inexperienced carbohydrate chemists.

Experimental and theoretical electron density distribution of alpha,alpha-trehalose dihydrate.

alpha,alpha-Trehalose is of interest because of its cryoprotective and antidessicant properties, and because it possesses various technical anomalies such as (13)C NMR spectra that give misleading indications of intramolecular structural symmetry. It is a non-reducing disaccharide, with the glycosidic oxygen atom shared by the anomeric carbon atoms of the two glucose rings, and is therefore subject to a proposed 'overlapping'exo-anomeric effect. We report here a study of the electron density of trehalose with X-ray diffraction and quantum mechanics calculations, similar to a recent study of sucrose, also a non-reducing molecule.

Conformational flexibility of soluble cellulose oligomers: chain length and temperature dependence.

Structures, dynamics, and stabilities of different sized cellulosic oligomers need to be considered when designing enzymatic cocktails for the conversion of biomass to biofuels since they can be both productive substrates and inhibitors of the overall process. In the present work, the conformational variability, hydrogen bonding, and mechanical properties of short, soluble cellulose chains are investigated as a function of chain length. Cellulose oligomers consisting 2, 4, and 6 beta-d-glucose units are examined in explicit solvent using replica exchange molecular dynamics (REMD) which provides a rigorous evaluation of the relative stabilities of different conformations and their temperature dependencies.

Comparison of different force fields for the study of disaccharides.

Eighteen empirical force fields and the semi-empirical quantum method PM3CARB-1 were compared for studying beta-cellobiose, alpha-maltose, and alpha-galabiose [alpha-D-Galp-(1-->4)-alpha-D-Galp]. For each disaccharide, the energies of 54 conformers with differing hydroxymethyl, hydroxyl, and glycosidic linkage orientations were minimized by the different methods, some at two dielectric constants. By comparing these results and the available crystal structure data and/or higher level density functional theory results, it was concluded that the newer parameterizations for force fields (GROMOS, GLYCAM06, OPLS-2005 and CSFF) give results that are reasonably similar to each other, whereas the older parameterizations for Amber, CHARMM or OPLS were more divergent.

Twisting of glycosidic bonds by hydrolases.

Patterns of scissile bond twisting have been found in crystal structures of glycoside hydrolases (GHs) that are complexed with substrates and inhibitors. To estimate the increased potential energy in the substrates that results from this twisting, we have plotted torsion angles for the scissile bonds on hybrid Quantum Mechanics::Molecular Mechanics energy surfaces. Eight such maps were constructed, including one for alpha-maltose and three for different forms of methyl alpha-acarviosinide to provide energies for twisting of alpha-(1,4) glycosidic bonds.

Evaluation of Density Functionals and Basis Sets for Carbohydrates.

Correlated ab initio wave function calculations using MP2/aug-cc-pVTZ model chemistry have been performed for three test sets of gas phase saccharide conformations to provide reference values for their relative energies. The test sets consist of 15 conformers of α- and β-d-allopyranose, 15 of 3,6-anhydro-4-O-methyl-d-galactitol, and four of β-d-glucopyranose. For each set, conformational energies varied by about 7 kcal/mol.

Neutron crystallography, molecular dynamics, and quantum mechanics studies of the nature of hydrogen bonding in cellulose Ibeta.

In the crystal structure of cellulose I beta, disordered hydrogen bonding can be represented by the average of two mutually exclusive hydrogen bonding schemes that have been designated A and B. An unanswered question is whether A and B interconvert dynamically, or whether they are static but present in different regions of the microfibril (giving temporally or a spatially averaged structures, respectively). We have used neutron crystallographic techniques to determine the occupancies of A and B at 295 and 15 K, quantum mechanical calculations to compare the energies of A and B, and molecular dynamics calculations to look at the stability of A.

Octa-O-propanoyl-beta-maltose: crystal structure, acyl stacking, related structures, and conformational analysis.

The crystal structure of beta-maltose octapropanoate (1) was solved to improve understanding of di-, oligo-, and polysaccharide conformations. The O6 and O6' atoms are in gg and gt orientations, respectively. Extrapolation of the coordinates of the non-reducing residue and observed linkage bond and torsion angles of 1 [Formula: see text] yields a left-handed helix similar to amylose triacetate I.

Linkage and pyranosyl ring twisting in cyclodextrins.

Acylated beta-cyclodextrins (beta-CDs) were studied to gain perspective on maltose octapropanoate, the crystal structure of which was reported in the preceding paper in this issue. Acylated beta-CDs are distorted so we looked at other CDs and gained increased understanding of distortion in CDs and possibly, shapes in starch. Classic CDs have six to eight glucose residues in a doughnut shape that is stabilized by a ring of inter-residue O3,,,O2' hydrogen bonds.

The external-anomeric torsional effect.

The rotational barrier for a methyl group at the end of an anomeric system is sometimes lower than we might have anticipated. Thus, in the trans-trans conformation of dimethoxymethane, the barrier to methyl rotation is calculated (B3LYP/6-311++G(2d,2p)) to be 2.22 kcal/mol, just slightly smaller than the corresponding barrier to rotation of the methyl group in methyl propyl ether of 2.

Determining the crystal structure of cellulose III(I) by modeling.

Recently, a one-chain monoclinic unit cell for cellulose III(I) having P2(1) symmetry and a single glucose in the asymmetric unit was proposed, based on high-resolution diffraction patterns. The new work challenged a two-chain structure that was published 25 years earlier, although it did not provide new three-dimensional coordinates. Our goals were to solve the structure by modeling, find whether modeling would reject the previously determined two-chain unit cell, and compare the model with the anticipated experimental structure.

Incremented alkyl derivatives enhance collision induced glycosidic bond cleavage in mass spectrometry of disaccharides.

Electrospray ionization and collision induced dissociation on a triple quadrupole mass spectrometer were used to determine the effect of spatial crowding of incremented alkyl groups of two anomeric pairs of peralkylated (methyl to pentyl) disaccharides (maltose/cellobiose and isomaltose/gentiobiose). Protonated molecules were generated which underwent extensive fragmentation under low energy conditions. For both the 1 --> 4 and 1 --> 6 alpha and beta isomers, at comparable collision energies the methyl derivative exhibited the least fragmentation followed by ethyl, propyl, butyl, and pentyl.

Crystal structure of penta-O-acetyl-beta-D-galactopyranose with modeling of the conformation of the acetate groups.

The crystal structure of penta-O-acetyl-beta-D-galactopyranose was determined with Mo K(alpha) radiation at 150 K to R = 0.029. The space group is P2(1)2(1)2(1), and the unit cell dimensions are, a = 8.

The crystal structure of the alpha-cellobiose.2 NaI.2 H(2)O complex in the context of related structures and conformational analysis.

The crystal structure of beta-D-glucopyranosyl-(1-->4)-alpha-D-glucopyranose (alpha-cellobiose) in a complex with water and NaI was determined with Mo K(alpha) radiation at 150 K to R=0.027. The space group is P2(1) and unit cell dimensions are a=9.