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The solution conformation of neocarrabiose 41-sulfate, which is a building block of κ-carrageenan, was investigated by a combination of molecular dynamics simulations and 1H NMR experiments. The calculated Ramachandran-type potential energy map for the glycosidic torsion angles φ and ψ of this dimer showed that there are two principal minimum-energy conformations, designated here as “a” and “b”. Comparison of the depths of these minima and the MD trajectories started from each minimum indicated that in a vacuum the molecular conformation in the “a” well is more stable than that in the “b” well. On the other hand, MD simulations in water showed that trajectories started from each minimum position stayed within their respective wells throughout the time courses of the simulations. However, analysis of the hydration water around the molecule indicated that the stability of the molecular conformation in the “a” well would be favored by solvation compared to the “b” well. Analysis of the experimental NOE−NMR d...

Molecular dynamics simulations employing umbrella sampling techniques have been used to calculate the potential of mean force (pmf) for the binding of a β-d-glucopyranose molecule to a benzene molecule in aqueous solution, as a model for the binding of sugar substrates to phenylalanine residues in proteins. The interaction of these two molecules was found to be strongly affected by hydration, as expected, with their nonpolar faces pairing by hydrophobic association to minimize the exposure of apolar groups to water. The pmf for the approach of these molecules is oscillatory in character, with two primary low-energy minima separated by a high free energy barrier, and with the net binding energy being approximately 1.1 kcal/mol and the intervening barrier being almost 2 kcal/mol. A third, weaker minimum was observed between 11 and 12 A. The oscillatory nature of the pmf results from the successive removal of water layers between the two molecules as they approach one another.

Molecular dynamics simulations employing adaptive umbrella sampling have been used to calculate the Ramachandran conformational potential of mean force in aqueous (TIP3P) solution for the α(1→4)-linked dimer of d-xylopyranose (4-O-α-d-xylopyranosyl-α-d-xylopyranose), a pentose analogue of maltose and a useful general model for the effects of solvent structuring upon biopolymer hydration. The vacuum adiabatic energy map for this molecule closely resembles that for maltose, but the solution pmf is quite different, with one of the principal vacuum minima almost completely disappearing in solution and with the global minimum-energy conformation being a new minimum which does not occur at all on the vacuum surface. This conformation is apparently stabilized by a water molecule which hydrogen bonds to a hydroxyl group on each ring, bridging between the two rings. The new conformation also places the two hydrophobic methylene groups almost in van der Waals contact, reducing their exposed surface area. Unfortunat...

Molecular mechanics calculations have been performed for the disaccharide neocarrabiose, one of the repeat units of beta-carrageenan, as a general model for the (1-->3)-linkage in the carrageenans. An adiabatic conformational energy map for this molecule has been prepared by constrained energy minimization and compared to previously reported relaxed maps. Neither the experimentally determined crystal structure of neocarrabiose nor the fiber diffraction conformation of iota-carrageenan is a low energy conformation on the relaxed Ramachandran map. Molecular dynamics simulations in vacuum produced trajectories consistent with this relaxed vacuum surface. However, a simulation with explicitly included solvent water molecules produced a trajectory that remained in the region of the two experimental structures. This dramatic solvation effect is apparently the result of the breaking of an interring hydrogen bond between the O2 hydroxyl groups of neocarrabiose as both groups hydrogen bond to solvent.

Recently, it was shown using structural neutron diffraction with isotopic substitutions (NDIS) measurements, combined with molecular dynamics simulations, that in an aqueous solution of D-xylose the hydroxyl group on the C4 position does not significantly occupy the position trans to the H4 atom. Here, a similar combination of NDIS and MD studies is described which uses D-xylose deuterated at the C5 position to further characterize this hydroxyl conformation as being trans to the C5 atom, as predicted by constrained MD simulations, confirming the previous study.

Limitations in experimental measurements complicate the investigations of biologically important disaccharides. Previous computational studies of disaccharides have been very CPU intensive. The application of simulated annealing to conformational space studies of disaccharides is shown to decrease the computational effort by more than an order of magnitude. At the same time this approach produces a more accurate description of the conformational space particularly in the high energy regions. The method is demonstrated on the biologically important GlcNac-β-(1-4)-GlcNac disaccharide and can be easily translated for application to other carbohydrates or related molecules. The energy surface E ( Π , ψ ) for the GlcNac-β-(1-4)-GlcNac disaccharide which is a function of the glycosidic linkage is analysed and compared to a similar surface generated by the standard computationally more intense exhaustive search method.

Molecular dynamics simulations have been used to model the flexibility of the seven-sugar oligosaccharide of the lectin from Erythrina corallodendron in three separate simulations: one of the isolated oligosaccharide in vacuo, one of the oligosaccharide in solution and one of the oligosaccharide linked to the protein in solution. Adiabatic conformational energy maps were prepared for each of the disaccharide linkages as a means of interpreting the observed dynamics and conformational averages in terms of intramolecular energy. The inclusion of aqueous solvent molecules appears to be necessary to reproduce the experimental conformational behavior, which also cannot be predicted well from conformational energy maps for the disaccharide linkages alone. The crystallographically determined conformation does not appear to be induced by the crystal dimerization, but is rather stable in solution. The build-up of fluctuations along the successive linkages of the oligosaccharide is significant and would be sufficient to prevent branch residues from being located in most crystal structure determinations. Good general agreement between the calculated solution structure and the average structure determined by NMR was found for most of the oligosaccharide linkages.

The structure of the lectin from Erythrina corallodendron (EcorL) has recently been solved crystallographically, with the oligosaccharide portion of this glycoprotein unusually well resolved. In general, the structure and dynamics of the oligosaccharides in glycoproteins are poorly understood. The crystal structure of EcorL provides an opportunity to probe the conformational properties of the oligosaccharide using computer modeling. Two 300 ps molecular dynamics simulations are reported of the oligosaccharide in solution isolated from the protein and bound to the protein and surrounded by water. The motions of the oligosaccharide are similar both free in solution and bonded to the protein. However, different parts of the glycosidic linkage conformational space have been explored by key component disaccharides in the two environments. The disaccharide of the “core” region shows greater flexibility in the isolated oligosaccharide than in the same region in the bound oligosaccharide. Because of the short length of these simulations, it could not be determined whether these differences are due to random chance or are a true reflection of the influence of the protein on the conformation of the oligosaccharide.

The structuring of solvent water by sugar solutes is studied using a molecular dynamics (MD) simulation of α- d -glucopyranose in aqueous (SPC) solution. The distribution of water positions actually observed in the MD simulation is compared to the solvent positions expected from a locally-tetrahedral distribution of hydrogen-bonded water molecules around the oxygen atoms. A reasonable correspondence between the observed and predicted hydration sites was found, but with certain deviations resulting from the incommensurate solvation requirements of adjacent functional groups. No evidence was found to support previous theories about sugar hydration which are based upon a supposed coincidence of the sugar structure with an assumed lattice-like model of liquid water. Solvent pair distribution functions were also used to characterize the observed water structuring, and methods of eliminating artificial minima in these distributions resulting from spherical averaging were examined.

Molecular mechanics calculations have been performed for the disaccharide carrabiose, one of the repeat units of β-carrageenan, as a general model for the (14)-linkage in the carrageenans. An adiabatic conformational energy map for this unsulfated molecule was prepared by constrained energy minimization and compared to a previously reported rigid-residue energy map for the sulfated molecule and to a similar adiabatic map for neocarrabiose, the related (13)-linked dimer repeat unit of β-carrageenan. Molecular dynamics simulations of this molecule in vacuo and in an aqueous (TIP3P) solution were calculated, and the observed motions were found to be generally consistent with the vacuum adiabatic energy map. Unlike the case observed in previous simulations of neocarrabiose, little salvation shift in the molecular conformation was observed for carrabiose. From the dynamics, the linkage was observed to be relatively flexible, as has been inferred from experiment on sulfated carrageenan polymers. © 1997 John Wiley & Sons, Inc.

Microcanonical ensemble molecular dynamics simulations have been used to examine the model dependence of the computed three-dimensional structuring which the typical sugar d-xylose imposes on surrounding solvent molecules in aqueous solution. The structuring imposed on water by biological solutes is quite complex, due to the complicated mix of chemical functionalities found in typical biopolymers, and has proven difficult to probe experimentally. Computer simulations have been the principal source of spatially resolved information about the solvent structuring about particular solutes, and previous simulations of this sugar have found configuration-dependent solvent structuring which appears to explain an important experimentally determined physical characteristic of the molecule, its anomeric ratio. Well-defined first and second solvation shells are observed around the sugar molecule with specific locations determined by the arrangement of functional groups in the solute. Here we examine the dependence o...

The method of intramolecular coordination number concentration invariance (ICNCI) is used on neutron diffraction with isotopic substitution (NDIS) measurements of aqueous solutions to separate the intra- and intermolecular contributions to the total intensities. Molecular dynamics simulations of corresponding systems are then used to interpret the ICNCI function. It is found that the ICNCI function (characterized by two concentration measurements) is sensitive specifically to intermolecular association and that the molecular dynamics can successfully replicate this function in the cases of the neutral species xylose and pyridine in aqueous solution. ICNCI functions can also be obtained by the addition of a cosolute (such as adding GdmCl or Gdm2SO4 to pyridine solutions). In that case it is found that molecular dynamics can replicate the ICNCI function for the addition of GdmCl to pyridine, but fails to successfully replicate the same function for the addition of Gdm2SO4. This result implies that the interaction of pyridine with guanidinium sulfate is over-estimated in these MD simulations, and is of significant importance to the use of molecular dynamics simulations to elucidate an atomic level understanding of the Hofmeister series.

Standard molecular dynamics (MD) and free energy simulations have been used to analyze the anomeric equilibrium for d-xylose in aqueous solution. This molecule was selected as a simple model for th...

The details of solution structure have proven difficult to probe experimentally, but computer simulations allow solvent structuring to be examined directly. We report here molecular dynamics (MD) simulations of a series of pentose sugars in solution, describe in detail the three-dimensional structuring which these molecules impose on water, and relate this structuring to the solute molecular topologies. Well-defined first and second solvation shells are observed around the sugar molecules with specific locations determined by the arrangement of functional groups within each solute. Calculated molecular internal energies and solvent interaction energies generally correspond qualitatively with earlier models of sugar energetics based on stability factors. However, pairs of axial hydroxyl groups on the same side of a sugar ring were found to be disfavored by solvation energy, not by internal energy, which is actually more favorable due to intramolecular hydrogen bonding, in accord with both quantum mechanica...

Free energy simulations and standard molecular mechanics calculations have been used to examine the binding specificity of the C-type lectin rat mannose-binding protein. This protein, which is important in inflammation and immunoglobin-independent immune response, recognizes and binds to mannose and high-mannose oligosaccharides but not to galactose. Molecular dynamics simulations were used to estimate the free energy difference between these two sugars in aqueous solution and in the binding site of the protein. While the simulations found mannose to be favored over galactose, interactions with the solvent tended to favor galactose. The calculated binding free energy difference for these two sugars to MBP was 3.1 kcal/mol favoring mannose, approximately twice the experimental value. An estimate of the resolution into components found that enthalpy favored mannose but that entropy favored galactose, a reversal of the situation in solution. From standard MD simulations, the galactose was found to rotate in ...

The interaction between a winter flounder antifreeze polypeptide and an ice/water interface was studied using Molecular Dynamics computer simulation techniques to study the mechanism of action of this class of antifreeze molecules. Simple Point Charge models were used for the water molecules, and a molecular mechanics program (CHARMM) was used to construct the model for the polypeptide. A (2021) face was exposed on the ice surface, as this is believed to be the experimentally favored ice face for peptide binding. The polypeptide binds strongly to the ice surface even though it was placed with its four polar threonine (Thr) groups pointing away from the ice surface. This tested the previously advanced hypothesis that adsorption occurs primarily between these groups and the ice due to a matching of the spacing between oxygen atoms in the ice lattice and the polar Thr residues. As well as contacts with other polar groups on the peptide, the binding to the ice produces a good steric fit of the peptide with the corrugated ice interface. The presence of the peptide did not induce any melting of the ice at 200 K.

Although it has a deceptively simple primary structure, the collective organization of bulk cellulose, particularly as it exists in cellulose fibers in the cell walls of living plants and other organisms, is quite diverse and complex. While some experimental techniques, such as vibrational spectroscopy and diffraction from partially crystalline samples, are able to provide insights into the organization of bulk cellulose, its intrinsic complexity has left many questions still unanswered. For this reason, additional probes of cellulose structure would be highly desirable. With the continuing advances in computer power through massive parallelization, and the steady progress in computer codes and force fields for modeling carbohydrate systems, molecular mechanics simulations have become an attractive means of studying cellulosic systems at the atomic and molecular level. The coming decade will almost certainly see remarkable advances in the understanding of cellulose using such simulations.

International audience; The microstructure evolution of confined glucose solutions in silica gels can provide insights into the effect of sugars in protecting living organisms under extreme dehydration conditions. Aqueous silica gels with relatively small pore sizes capable of deforming under changes in environmental conditions are used here as a model system. In situ monitoring of the dehydration process − with and without the presence of sugar molecules − by optical photography, gravimetric measurements, small-angle neutron scattering, and atomic force microscopy reveals that sugar plays a crucial role in the mechanics and protection of the gel. In the absence of sugar, dehydration leads to considerable degradation, whereas the incorporation of large doses of glucose maintains the stability and robustness of the structure. A model is proposed to explain the time dependence of the dehydration process

Although it has a deceptively simple primary structure, the collective organization of bulk cellulose, particularly as it exists in cellulose fibers in the cell walls of living plants and other organisms, is quite diverse and complex. While some experimental techniques, such as vibrational spectroscopy and diffraction from partially crystalline samples, are able to provide insights into the organization of bulk cellulose, its intrinsic complexity has left many questions still unanswered. For this reason, additional probes of cellulose structure would be highly desirable. With the continuing advances in computer power through massive parallelization, and the steady progress in computer codes and force fields for modeling carbohydrate systems, molecular mechanics simulations have become an attractive means of studying cellulosic systems at the atomic and molecular level. The coming decade will almost certainly see remarkable advances in the understanding of cellulose using such simulations.

International audience; The pathway for pyranose ring conformational transitions in both anomers of glucose has been studied using molecular mechanics calculations both in vacuum and in aqueous (SPC/E) solution. The pathway for the transition in vacuum from the 4C1 to the 1C4 chair conformations in a-D-glucopyranose was found to proceed over a low barrier between the 4E and E5 conformers, and centred almost on 4H5, and then downhill through the 1S5 conformation to 1C4. A dead end pathway, with no early barrier, was found to lead to the 5S1 conformation, which thus would represent a kinetic trap impeding interconversion to the opposite chair in vacuum. Hydration was found to significantly lower the transition barriers, and in particular, to make the blocked pathway though 5S1 is feasible at lower temperatures. Transitions between the chair forms for the b-anomer of glucopyranose were in general found to be somewhat more facile, and to exhibit less influence from the presence of solvent.

Molecular dynamics and energy minimization computer modeling calculations have been used to study the conformational behavior of the prototypical triglyceride molecule trilaurin. The energy of an isolated molecule was minimized using both the QuantdCHARMm force field and a newly developed CFF parametrization for comparisons. The crystal structure was found to be a locally stable geometry using CHARMm, but with the CFF potential the structure collapsed into a geometry with C3 symmetry similar to the hypothesized bilayer structure with all three aliphatic chains on the same side of the glycerol backbone. A full molecular dynamics simulation of a trilaurin molecule in aqueous solution, starting in the crystal structure, was also performed. This “tuning fork structure was found to undergo a slow drift in solution toward a more compact geometry, but it was not possible to simulate the system for a sufficient period to determine whether this process was completed or would continue until a geometry similar to the CFF structure was reached. The triglyceride-water interactions were found to be consistent with the behavior expected for a predominantly hydrophobic species containing a polar headgroup consisting of hydrogen-bondaccepting oxygen atoms.

The functional performance of the whey protein β-lactoglobulin has been improved by the application of a rational design strategy and the use of site-directed mutagenesis to implement it. Three functional properties of β-lactoglobulin have been investigated: its ability to bind retinol; its tendency to form aggregates upon heating; and its ability to form thermoset gel networks. Any improvements made to β-lactoglobulin that enhance its performance during food processing will have a profound effect on its economic value. Such improvements, coupled with the ability to express them in dairy cattle, will increase the food and other applications of this protein as an ingredient, and open new markets for the use of whey proteins.

Recent advances in computer speeds now make possible the use of numerical simulations to model directly the relationships between molecular structure and functional properties. Molecular mechanics calculations, particularly molecular dynamics and Monte Carlo simulations, have long been used to study aqueous systems, and have played a crucial role in advancing our understanding of liquid water. It is also possible to use such computer simulations to study the interactions of solvent water with food molecules, which allows the direct theoretical examination of the structural basis for solution properties. We have conducted a series of such studies of several prototypical carbohydrates in aqueous solution. Solvent interactions were found to have significant effects on the conformational behavior of carbohydrates, and different solutes were found to have different effects upon the solvent behavior. The nature of the interaction of water with carbohydrate functional groups was found to depend not only upon the nature of the functional group, but also upon its location in the molecule relative to other functional groups. Hydrogen bonding is particularly important in carbohydrates, and was found to play a complex role in determining solution properties and conformation.

Modern biophysics has benefited greatly from the use of X-ray and neutron diffraction from ordered single crystals of proteins and other macromolecules to give highly detailed pictures of these molecules in the solid state. However, the most biologically relevant environments for these molecules are liquid solutions, and their liquid state properties are sensitive to details of the liquid structuring. The best experimental method for studying such structuring is also neutron diffraction, but of course, the inherent disorder of the liquid state means that these experiments cannot hope to achieve the level of informational detail available from single crystal diffraction. Nonetheless, recent advances in neutron beam intensity, beam stability, and detector sensitivity mean that it should be possible, at least in principle, to use such measurements to extract information about structuring in much more complex systems than have previously been studied. We describe a series of neutron diffraction studies of isotopically labeled molecules in aqueous solution which, when combined with results from computer simulations, can be used to extract conformational information of the hydration of the molecules themselves, essentially opening up new avenues of investigation in structural biology.

Molecular dynamics simulations were carried out on a concentrated system of β- d -glucopyranose and imidazole molecules in a periodic box of water at 298 K. The purpose of the simulations was to determine whether or not there was any tendency for these two solutes to associate in an aqueous environment, as has previously been observed for other planar functional groups from amino acid side chains, such as the indole group of tryptophan or the phenolic group of tyrosine. A weak stacking interaction between β- d -glucopyranose, as a model for cellulose, and imidazole was indeed observed, with an energy of ∼0.25 kcal/mol per pair, less than kT. Somewhat surprisingly, considerable imidazole self-association into small aggregates (dimers and trimers) was also observed, with binding energies of ∼0.4 kcal/mol per pair, although still less than kT. Considerable non-stacked interactions between glucose and imidazole through hydrogen bonding were also found. These hydrogen bonds primarily involved the N3 atom of imidazole, because the N–H group of N1 was insufficiently polar to compete for water hydrogen bond partners.

We use molecular simulation to elucidate the structural behavior of small hydrated cellulose Iβ microfibrils heated to 227 °C (500 K) with two carbohydrate force fields. In contrast to the characteristic two-dimensional hydrogen-bonded layer sheets present in the cellulose Iβ crystal structure, we show that at high temperature a three-dimensional hydrogen bond network forms, made possible by hydroxymethyl groups changing conformation from trans-gauche (TG) to gauche-gauche (GG) in every second layer corresponding to "center" chains in cellulose Iβ and from TG to gauche-trans (GT) in the "origin" layer. The presence of a regular three-dimensional hydrogen bond network between neighboring sheets eliminates the possibility of twist, whereas two-dimensional hydrogen bonding allows for microfibril twist to occur. Structural features of this high-temperature phase as determined by molecular simulation may explain several experimental observations for which no detailed structural basis has been offered. This includes an explanation for the observed temperature and crystal size dependence for the extent of hydrogen/deuterium exchange, and diffraction patterns of cellulose at high temperature.

International audience; Glucose aqueous solutions con!ned in MCM-41 cylindrical pores of diameter 3.2 nm have been studied by molecular dynamics (MD) simulations and quasielastic neutron scattering (QENS). MD simulations reveal a strong preferential interaction of glucose molecules with the silica walls, which induces signi!cant concentration gradients within the pore. The in"uence of glucose on the structural and dynamical properties of water strongly depends on the region of the pore considered. The distortion of the hydrogen bond network (HBN) and of the tetrahedral organization of interfacial water molecules induced by silica is much stronger than that induced by glucose molecules. The interfacial glucose molecules di#use about 1 order of magnitude slower than those in the core region. Di#erences in a$nities for silica of the di#erent species in con!ned hydrogen-bonded mixtures induce signi!cant structural and dynamical heterogeneities not present in bulk solutions.

Molecular dynamics simulations were carried out for a system consisting of the carbohydrate-binding module (CBM) of the cellulase CBH I from Trichoderma reesei (Hypocrea jecorina) in a concentrated solution of β-D-glucopyranose, to determine whether there is any tendency for the sugar molecules to bind to the CBM. In spite of the general tendency of glucose to behave as an osmolyte, a marked tendency for the sugar molecules to bind to the protein was observed. However, the glucose molecules tended to bind only to specific sites on the protein. As expected, the hydrophobic face of the sugar molecules, comprising the axial H1, H3, and H5 aliphatic protons, tended to adhere to the flat faces of the three tyrosine side chains on the planar binding surface of the CBM. However, a significant tendency to bind to a groove-like feature on the upper surface of the CBM was also observed. These results would not be inconsistent with a model of the mechanism for this globular domain in which the cellodextrin chain being removed from the surface of crystalline cellulose passes over the upper surface of the CBM, presumably then available for hydrolysis in the active site tunnel of this processive cellulase.

A winter flounder antifreeze polypeptide (HPLC-6) has been studied in vacuo and in aqueous solution using molecular dynamics computer simulation techniques. The helical conformation of this polypeptide was found to be stable both in vacuum and in solution. The major stabilizing interactions were found to be the main-chain hydrogen bonds, a salt-bridge interaction, and solute-solvent hydrogen bonds. A significant bending in the middle of the polypeptide chain was observed both in vacuo and in solvent at 300 K. Possible causes of the bending are discussed. From simulations of mutant polypeptide molecules in vacuo, it is concluded that the bend in the native polypeptide was caused by side chain to backbone hydrogen bond competition involving the Thr 24 side chain and facilitated by strains on the helix resulting from the Lys 18-Glu 22 salt bridge.

Molecular dynamics simulations of pure water employing two different empirical water models have been used to study the effects of different methods for truncation of long-range interactions in molecular mechanics calculations. As has been observed previously in integral equation studies, “shifting” these interactions on an atom-by-atom basis was found to produce artificial structuring in the water and affect diffusion rates. In cases where some form of short-range truncation must be used, the ST2 switching function applied on a group-by-group basis was found to be the most realistic procedure. If atom-based shifting must be employed, a cutoff distance greater than or equal to 12.0 A was found to be required to produce realistic results. © 1993 John Wiley & Sons, Inc.

Molecular dynamics simulations of maltose in two different conformations in vacuum and aqueous (TIP3P) solution have been used to examine the types of hydrogen bonds made by this carbohydrate molecule. Maltose was found to be extensively hydrogen bonded to solvent molecules in aqueous solution, and these hydrogen bonds were found to have potential conformational consequences. The exchange of an intramolecular O2-O3' hydrogen bond found in the crystal structure for hydrogen bonds to solvent was observed to produce significant changes in the solvation of the sugar molecule

Multidimensional potentials of mean force for the interactions in aqueous solution of both anomers of D-glucopyranose with two planar aromatic molecules, indole and para-methyl-phenol, have been calculated using molecular dynamics simulations with umbrella sampling and were subsequently used to estimate binding free energies. Indole and para-methyl-phenol serve as models for the side chains of the amino acids tryptophan and tyrosine, respectively. In all cases, a weak affinity between the glucose molecules and the flat aromatic surfaces was found. The global minimum for these interactions was found to be for the case when the pseudoplanar face of β-D -glucopyranose is stacked against the planar surfaces of the aromatic residues. The calculated binding free energies are in good agreement with both experiment and previous simulations. The multidimensional free energy maps suggest a mechanism that could lend kinetic stability to the complexes formed by sugars bound to sugar-binding proteins.

Molecular dynamics simulations have been used to calculate the potentials of mean force for separating short cellooligomers in aqueous solution as a means of estimating the contributions of hydrophobic stacking and hydrogen bonding to the insolubility of crystalline cellulose. A series of four potential of mean force (pmf) calculations for glucose, cellobiose, cellotriose, and cellotetraose in aqueous solution were performed for situations in which the molecules were initially placed with their hydrophobic faces stacked against one another, and another for the cases where the molecules were initially placed adjacent to one another in a co-planar, hydrogen-bonded arrangement, as they would be in cellulose Ibeta. From these calculations, it was found that hydrophobic association does indeed favor a crystal-like structure over solution, as might be expected. Somewhat more surprisingly, hydrogen bonding also favored the crystal packing, possibly in part because of the high entropic cost for hydrating glucose hydroxyl groups, which significantly restricts the configurational freedom of the hydrogen-bonded waters. The crystal was also favored by the observation that there was no increase in chain configurational entropy upon dissolution, because the free chain adopts only one conformation, as previously observed, but against intuitive expectations, apparently due to the persistence of the intramolecular O3-O5 hydrogen bond.

International audience; Molecular dynamics simulations of water confined in two hydrophilic cylindrical pores--PH and PL-- that differ in their silanol surface concentration (7.6 and 3.0 nm−2, respectively) have been performed at 300 K. A strong interaction of interfacial water molecules with the pore was systematically found and gives rise to a layering effect, a significant distortion of both the hydrogen bond network (HBN) and the tetrahedral structure of these water molecules, and a corresponding subdiffusive mean square displacement along the main axis of the pores. By contrast, water molecules in the inner part of both pores were found to behave similarly to bulk water. The HBN and the tetrahedral configuration of water were more gradually distorted in the PL pore given the larger heterogeneity and rugosity of the surface, and the number of water-pore hydrogen bonds did not scale linearly with the silanol surface concentration of the pores, in part because of the close proximity between silanols in the PH pore. With the PL pore, the dynamic slowing down of water was found consistent with the experiment, suggesting that it provides a better model for the cylindrical MCM-41 mesopores. The structural and dynamical properties of water vary little with the silica force field.

Cellulose is the homopolymer of (1 {yields} 4)-{beta}-D-glucose. The chemical composition of this polymer is simple, but understanding the conformation and packing of cellulose molecules is challenging. This chapter describes the structure of cellulose from the perspective of molecular mechanics simulations, including conformational analysis of cellobiose and simulations of hydrated cellulose I{beta} with CSFF and GLYCAM06, two sets of force field parameters developed specifically for carbohydrates. Many important features observed in these simulations are sensitive to differences in force field parameters, giving rise to dramatically different structures. The structures and properties of non-naturally occurring cellulose allomorphs (II, III, and IV) are also discussed.

Molecular dynamics computer simulations have been carried out on aqueous solutions of glucose at concentrations bracketing those previously measured with quasi-elastic neutron scattering (QENS), in order to investigate the motions and interactions of the sugar and water molecules. In addition, QENS measurements have been carried out on fructose solutions to determine whether the effects previously observed for glucose apply to monosaccharide solutions. The simulations indicate a dynamical analogy between higher solute concentration and lower temperature that could provide a key explanation of the bioprotective phenomena observed in many living organisms. The experimental results on fructose solutions show qualitatively similar behavior to the glucose solutions. The dynamics of the water molecules are essentially the same, while the translational diffusion of the sugar molecules is slightly faster in the fructose solutions.

International audience; Molecular dynamics simulations of a 3 molal aqueous solution of d-sorbitol (also called d-glucitol) have been performed at 300 K, as well as at two elevated temperatures to promote conformational transitions. In principle, sorbitol is more flexible than glucose since it does not contain a constraining ring. However, a conformational analysis revealed that the sorbitol chain remains extended in solution, in contrast to the bent conformation found experimentally in the crystalline form. While there are 243 staggered conformations of the backbone possible for this open-chain polyol, only a very limited number were found to be stable in the simulations. Although many conformers were briefly sampled, only eight were significantly populated in the simulation. The carbon backbones of all but two of these eight conformers were completely extended, unlike the bent crystal conformation. These extended conformers were stabilized by a quite persistent intramolecular hydrogen bond between the hydroxyl groups of carbon C-2 and C-4. The conformational populations were found to be in good agreement with the limited available NMR data except for the C-2–C-3 torsion (spanned by the O-2–O-4 hydrogen bond), where the NMR data support a more bent structure.

The application of molecular dynamics simulations to the modeling of oligosaccharides has opened up significant new areas of investigation in carbohydrate structural studies. In the past year, a number of simulations of carbohydrate flexibility and solvation have appeared using these techniques, which offer the hope of resolving many intractable questions concerning oligosaccharide conformational structure.

The calculated free energy difference is the result of near cancelation of two larger, statistically significant contributions, i.e., an intramolecular electrostatic term favoring the α anomer and an intermolecular solute-solvent interaction term favoring the β anomer. This result supports the conjecture that solvation stabilizes the β anomer in water. There is a large difference in the intramolecular contribution to the anomeric equilibrium calculated in solution from the free energy simulation and the gas-phase minimum; this suggests that conformational averaging, modulated by the solvent, is significant even for the internal terms. An examination of the rotamer distribution in the hydroxymethyl side chain shows that the trans, gauche conformer is strongly disfavored in aqueous solution, in accord with experiment

Neutron diffraction experiments were carried out on concentrated aqueous solutions of beryllium chloride at three concentrations: 1.5, 3, and 6 molal. By working with a specific ("null") mixture of heavy water (D2O) and water (H2O), information on the local structure around Be2+ ions was extracted directly. For all three BeCl2 solutions, the results show that the Be2+ ion has a well-defined 4-fold coordination shell that is dominated by oxygen atoms. There is also a relatively small probability (10-15%) that there are direct contacts between Be2+ and Cl- at a distance of approximately 2.2 angstroms. The oxygen atoms of the highly structured Be2+ first hydration shell are found to be situated at 2.6 angstroms apart, and form a pyramidal structure, in agreement with recent MD simulation results. The Cl- ions have approximately seven oxygen atoms (water molecules) in their hydration shells sited at 3.2 angstroms.

Molecular dynamics simulations have been used to study the motions in vacuum of the disaccharide sucrose. Ensembles of trajectories were calculated for each of the five local minimum energy conformations identified in the adiabatic conformational energy mapping of this molecule. The model sucrose molecules were found to exhibit a variety of motions, although the global minimum energy conformation was found to be dynamically stable, and no transitions away from this structure were observed to occur spontaneously. In all but one of these vacuum trajectories, the intramolecular hydrogen bond between residues was maintained, in accord with recent nmr studies of this molecule in aqueous solution. Considerable flexibility of the furanoid ring was found in the trajectories. No "flips" to the opposite puckering for this ring were found in the simulations starting from the global minimum, although such a transition was observed for a trajectory initiated with one of the higher local minimum energy conformations. Overall, the observed structural fluctuations were consistent with the experimental picture of sucrose as a relatively rigid molecule.

The dynamics of trehalose molecules in aqueous solutions confined in silica gel have been studied by quasielastic neutron scattering (QENS). Small-angle neutron scattering measurements confirmed the absence of both sugar clustering and matrix deformation of the gels, indicating that the results obtained are representative of homogeneous trehalose solutions confined in a uniform matrix. The pore size in the gel is estimated to be 18 nm, comparable to the distances in cell membranes. For the QENS measurements, the gel was prepared from D2O in order to accentuate the scattering from the trehalose. Values for the translational diffusion constant and effective jump distance were derived from model fits to the scattering function. Comparison with QENS and NMR results in the literature for bulk trehalose shows that confinement on a length scale of 18 nm has no significant effect on the translational diffusion of trehalose molecules.

Cellobiohydrolases are the most effective single component of fungal cellulase systems; however, their molecular mode of action on cellulose is not well understood. These enzymes act to detach and hydrolyze cellodextrin chains from crystalline cellulose in a processive manner, and the carbohydrate-binding module (CBM) is thought to play an important role in this process. Understanding the interactions between the CBM and cellulose at the molecular level can assist greatly in formulating selective mutagenesis experiments to confirm the function of the CBM. Computational molecular dynamics was used to investigate the interaction of the CBM from Trichoderma reesei cellobiohydrolase I with a model of the (1,0,0) cellulose surface modified to display a broken chain. Initially, the CBM was located in different positions relative to the reducing end of this break, and during the simulations it appeared to translate freely and randomly across the cellulose surface, which is consistent with its role in processivity. Another important finding is that the reducing end of a cellulose chain appears to induce a conformational change in the CBM. Simulations show that the tyrosine residues on the hydrophobic surface of the CBM, Y5, Y31 and Y32 align with the cellulose chain adjacent to the reducing end and, importantly, that the fourth tyrosine residue in the CBM (Y13) moves from its internal position to form van der Waals interactions with the cellulose surface. As a consequence of this induced change near the surface, the CBM straddles the reducing end of the broken chain. Interestingly, all four aromatic residues are highly conserved in Family I CBM, and thus this recognition mechanism may be universal to this family.